Case report: Levodopa challenge test is important in identifying dopamine-induced freezing of gait in patient with Parkinson's disease.

Introduction: Freezing of gait (FOG) is a disabling and heterogeneous symptom in patients with Parkinson's disease (PD). Among them, dopamine-induced FOG is rare and difficult to identify. The treatment of dopamine-induced FOG is complex. Case presentation: We herein presented a case of PD patient who complicated with refractory FOG. It was identified as dopamine-induced FOG during levodopa challenge test. Her symptoms were alleviated after we reduced the total equivalent dosage of levodopa. Conclusion: Our report emphasizes the importance of levodopa challenge test in identifying different types of FOG, which is very important for further adjusting treatment.

LAMTOR1/mTORC1 promotes CD276 to induce immunosuppression via PI3K/Akt/MMP signaling pathway in Clostridium perfringens-induced necrotic enteritis of laying hens.

Clostridium perfringens (C. perfringens) causes avian necrotic enteritis, leading to huge economic losses to the poultry industry. This pathogen induces host immunosuppression; however, the molecular mechanism is still unclear. Thus, we established a laying hen infection model to explore this mechanism. We randomly divided 20 one-old-day laying hens into the control and infection groups. The infection group was infected intragastrically with 1 × 109 colony-forming units of C. perfringens in 1 mL of sterile phosphate-buffered saline (PBS) once a day from d 17 to 20; the control group received the same volume of PBS without the bacterium. Twenty-four hours after the last challenge, we sacrificed the laying hens and collected the jejunum for analysis. The infection group presented alterations in blood biochemical parameters and necrotic lesion scores as well as damage to the jejunum. Proteomics revealed 427 upregulated and 291 downregulated proteins in the infection group. In the infection group, CD3, CD4, and CD8 messenger RNA expression (mRNA) expression was decreased; LAMTOR1 and mTORC1 mRNA expression was increased; CD276 protein expression was enhanced; and the PI3K/Akt/MMP pathway was activated in jejunum of laying hens. This is the first study to report CD276 expression in the jejunum related to immunosuppression in a laying hen model of necrotic enteritis. It provides some new key targets to potentially control avian necrotic enteritis.

Hydrogel Microneedle Patches Loaded with Stem Cell Mitochondria-Enriched Microvesicles Boost the Chronic Wound Healing.

Rescuing or compensating mitochondrial function represents a promising therapeutic avenue for radiation-induced chronic wounds. Adult stem cell efficacies are primarily dependent on the paracrine secretion of mitochondria-containing extracellular vesicles (EVs). However, effective therapeutic strategies addressing the quantity of mitochondria and mitochondria-delivery system are lacking. Thus, in this study, we aimed to design an effective hydrogel microneedle patch (MNP) loaded with stem cell-derived mitochondria-rich EVs to gradually release and deliver mitochondria into the wound tissues and boost wound healing. We, first, used metformin to enhance mitochondrial biogenesis and thereby increasing the secretion of mitochondria-containing EVs (termed "Met-EVs") in adipose-derived stem cells. To verify the therapeutic effects of Met-EVs, we established an in vitro and an in vivo model of X-ray-induced mitochondrial dysfunction. The Met-EVs ameliorated the mitochondrial dysfunction by rescuing mitochondrial membrane potential, increasing adenosine 5'-triphosphate levels, and decreasing reactive oxygen species production by transferring active mitochondria. To sustain the release of EVs into damaged tissues, we constructed a Met-EVs@Decellularized Adipose Matrix (DAM)/Hyaluronic Acid Methacrylic Acid (HAMA)-MNP. Met-EVs@DAM/HAMA-MNP can load and gradually release Met-EVs and their contained mitochondria into wound tissues to alleviate mitochondrial dysfunction. Moreover, we found Met-EVs@DAM/HAMA-MNP can markedly promote macrophage polarization toward the M2 subtype with anti-inflammatory and regenerative functions, which can, in turn, enhance the healing process in mice with skin wounds combined radiation injuries. Collectively, we successfully fabricated a delivery system for EVs, Met-EVs@DAM/HAMA-MNP, to effectively deliver stem cell-derived mitochondria-rich EVs. The effectiveness of this system has been demonstrated, holding great potential for chronic wound treatments in clinic.

Joint modeling of longitudinal health-related quality of life during concurrent chemoradiotherapy period and long-term survival among patients with advanced nasopharyngeal carcinoma.

BACKGROUND: To investigate the prognosis of longitudinal health-related quality of life (HRQOL) during concurrent chemoradiotherapy (CCRT) on survival outcomes in patients with advanced nasopharyngeal carcinoma (NPC). METHODS: During 2012-2014, 145 adult NPC patients with stage II-IVb NPC were investigated weekly using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire core 30 (EORCT QLQ-C30) during their CCRT period. The effects of longitudinal trends of HRQOL on survival outcomes were estimated using joint modeling, and hazard ratios (HRs) with 95% confidence intervals (95% CIs) were reported as a 10-point increase in HRQOL scores. RESULTS: After a median follow-up of 83.4 months, the multivariable models showed significant associations of longitudinal increasing scores in fatigue and appetite loss during the CCRT period with distant metastasis-free survival: 10-point increases in scores of fatigue and appetite loss domains during CCRT period were significantly associated with 75% (HR: 1.75, 95% CI: 1.01, 3.02; p = 0.047) and 59% (HR: 1.59, 95% CI: 1.09, 2.59; p = 0.018) increase in the risk of distant metastasis, respectively. The prognostic effects of the longitudinal HRQOL trend on overall survival and progress-free survival were statistically non-significant. CONCLUSION: Increases in fatigue and appetite loss of HRQOL during the CCRT period are significantly associated with high risks of distant metastasis in advanced NPC patients. Nutritional support and psychological intervention are warranted for NPC patients during the treatment period.

Interaction between economic status and healthy lifestyle in long COVID among Chinese older population: a cross-sectional study.

OBJECTIVES: To estimate the interaction between economic status (ES) and healthy lifestyle in long COVID among Chinese older people infected with SARS-CoV-2. DESIGN: A cross-sectional study based on the Peking University Health Cohort in Anning, Yunnan. SETTING: All primary health institutions in Anning, Yunnan Province, China, from April to May 2023. PARTICIPANTS: A total of 4804 people aged 60 and older infected with SARS-CoV-2 were included in this study. PRIMARY AND SECONDARY OUTCOME MEASURES: Long COVID was measured by participants' self-reported symptoms using structured questionnaires. ES was measured by last-month personal income, and participants' ES was defined as low if their income was below the per capita monthly income of local residents. Lifestyle score was equal to the number of healthy behaviours (including smoking, drinking, weight, exercise and diet) and grouped using the median score as the cut-off point. Univariate and multivariate logistic models were employed to estimate the association of ES with long COVID. Interaction between ES and lifestyle in long COVID was assessed by multiplicative interaction term. RESULTS: We enrolled a total of 4804 participants infected with SARS-CoV-2, of whom 57.3% (2754 of 4804) had at least one long COVID symptom. Fatigue (1546, 56.1%), cough (1263, 45.9%) and muscle pain (880, 32.0%) were the top three common symptoms. Patients with low ES had a 48% (adjusted OR: 1.48; 95% CI 1.22, 1.82) increased risk of long COVID. A significant interaction was observed between ES and lifestyle (p value for interaction <0.001) in long COVID. CONCLUSION: The interaction between ES and healthy lifestyle in long COVID was prominent. Comprehensive strengthened economic support for patients recovering from COVID-19, especially for those with low healthy lifestyle, should be implemented to prevent and manage long COVID symptoms.

Angelica sinensis polysaccharide facilitates chondrogenic differentiation of adipose-derived stem cells via MDK-PI3K/AKT signaling cascade.

OBJECT: Adipose-derived mesenchymal stem cells (ADSCs) have received significant attention in the field of cartilage tissue repair. Angelica sinensis polysaccharide (ASP) can enhance both the proliferation and differentiation of mesenchymal stem cells. Therefore, we intend to explore the effect of ASP on chondrogenic differentiation of ADSCs in vitro, and elucidate the underlying mechanisms. METHOD: ADSCs were treated with different concentrations of ASP to determine the optimal concentration. The chondrogenic differentiation of ADSCs was evaluated using Alcian blue staining, qRT-PCR, western blot, and IF staining. Transcriptome sequencing was performed to identify the expression profiles of ADSCs before and after ASP treatment, followed by bioinformatic analyses including differential expression analysis, enrichment analysis, and construction of PPI networks to identify differentially expressed genes (DEGs) associated with ASP and chondrogenic differentiation. RESULT: Surface markers of isolated rat-derived ADSCs were identified by CD44+CD90+CD45-CD106-, and exhibited the capacity for lipogenic, osteogenic, and chondrogenic differentiation. With increasing concentration of ASP treatment, there was an upregulation in the activity and acidic mucosubstance of ADSCs. The levels of Aggrecan, COL2A1, and Sox9 showed an increase in ADSCs after 28 days of 80 µg/ml ASP treatment. Transcriptome sequencing revealed that ASP-associated DEGs regulate extracellular matrix synthesis, immune response, inflammatory response, and cell cycle, and are involved in the NF-κB, AGE-RAGE, and calcium pathways. Moreover, Edn1, Frzb, Mdk, Nog, and Sulf1 are hub genes in DEGs. Notably, ASP upregulated MDK levels in ADSCs, while knockdown of MDK mitigated ASP-induced elevations in acidic mucosubstance, chondrogenic differentiation-related markers (Aggrecan, COL2A1, and Sox9), and the activity of the PI3K/AKT pathway. CONCLUSION: ASP enhances the proliferation and chondrogenic differentiation of ADSCs by activating the MDK-mediated PI3K/AKT pathway.

Performance of radiomics in the differential diagnosis of parotid tumors: a systematic review.

Purpose: A systematic review and meta-analysis were conducted to evaluate the diagnostic precision of radiomics in the differential diagnosis of parotid tumors, considering the increasing utilization of radiomics in tumor diagnosis. Although some researchers have attempted to apply radiomics in this context, there is ongoing debate regarding its accuracy. Methods: Databases of PubMed, Cochrane, EMBASE, and Web of Science up to May 29, 2024 were systematically searched. The quality of included primary studies was assessed using the Radiomics Quality Score (RQS) checklist. The meta-analysis was performed utilizing a bivariate mixed-effects model. Results: A total of 39 primary studies were incorporated. The machine learning model relying on MRI radiomics for diagnosis malignant tumors of the parotid gland, demonstrated a sensitivity of 0.80 [95% CI: 0.74, 0.86], SROC of 0.89 [95% CI: 0.27-0.99] in the validation set. The machine learning model based on MRI radiomics for diagnosis malignant tumors of the parotid gland, exhibited a sensitivity of 0.83[95% CI: 0.76, 0.88], SROC of 0.89 [95% CI: 0.17-1.00] in the validation set. The models also demonstrated high predictive accuracy for benign lesions. Conclusion: There is great potential for radiomics-based models to improve the accuracy of diagnosing benign and malignant tumors of the parotid gland. To further enhance this potential, future studies should consider implementing standardized radiomics-based features, adopting more robust feature selection methods, and utilizing advanced model development tools. These measures can significantly improve the diagnostic accuracy of artificial intelligence algorithms in distinguishing between benign and malignant tumors of the parotid gland. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023434931.

Deep learning enhancing guide RNA design for CRISPR/Cas12a-based diagnostics.

Rapid and accurate diagnostic tests are fundamental for improving patient outcomes and combating infectious diseases. The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) Cas12a-based detection system has emerged as a promising solution for on-site nucleic acid testing. Nonetheless, the effective design of CRISPR RNA (crRNA) for Cas12a-based detection remains challenging and time-consuming. In this study, we propose an enhanced crRNA design system with deep learning for Cas12a-mediated diagnostics, referred to as EasyDesign. This system employs an optimized convolutional neural network (CNN) prediction model, trained on a comprehensive data set comprising 11,496 experimentally validated Cas12a-based detection cases, encompassing a wide spectrum of prevalent pathogens, achieving Spearman's ρ = 0.812. We further assessed the model performance in crRNA design for four pathogens not included in the training data: Monkeypox Virus, Enterovirus 71, Coxsackievirus A16, and Listeria monocytogenes. The results demonstrated superior prediction performance compared to the traditional experiment screening. Furthermore, we have developed an interactive web server (https://crispr.zhejianglab.com/) that integrates EasyDesign with recombinase polymerase amplification (RPA) primer design, enhancing user accessibility. Through this web-based platform, we successfully designed optimal Cas12a crRNAs for six human papillomavirus (HPV) subtypes. Remarkably, all the top five predicted crRNAs for each HPV subtype exhibited robust fluorescent signals in CRISPR assays, thereby suggesting that the platform could effectively facilitate clinical sample testing. In conclusion, EasyDesign offers a rapid and reliable solution for crRNA design in Cas12a-based detection, which could serve as a valuable tool for clinical diagnostics and research applications.

Heterotopic pancreas in the gallbladder: A case report.

BACKGROUND: Heterotopic pancreas (HP) refers to pancreatic tissue located in areas with no vascular or anatomical connection to the pancreas. HP occurs mostly in the stomach, duodenum, and colon, and rarely in the gallbladder. CASE SUMMARY: A 57-year-old woman was referred to our hospital complaining of right upper quadrant discomfort for 3 years. An abdominal computed tomography scan revealed adenomyomatosis with a thickened fundus of the gallbladder. The patient underwent a laparoscopic cholecystectomy, and pathological examination unexpectedly showed heterotopic pancreatic tissue in the gallbladder. The patient had a favorable recovery and was discharged on postoperative day 3. She did not report any symptoms or complications at the 6-mo postoperative follow-up. Pathologists should pay close attention to such pancreatic tissue and carefully examine it for dysplasia or malignancy. CONCLUSION: This case provides more information about HP in the gallbladder, a rare occurrence.

Feline dystrophin-deficient muscular dystrophy misdiagnosed as Toxoplasma myositis.

Case summary: A 6-month-old male entire domestic shorthair cat presented for presumptive Toxoplasma myopathy that was non-responsive to antiprotozoal therapy. Clinical features included marked macroglossia, dysphagia, regurgitation, truncal muscle hypertrophy, pelvic limb gait abnormalities and megaoesophagus. Relevant diagnostics included serial creatine kinase activity, cardiac troponin I, fluoroscopic swallow study and routine muscle histopathology. Ultimately, post-mortem histopathology with immunostaining demonstrated markedly decreased or absent staining for the rod and carboxy terminus of dystrophin, confirming a dystrophin-deficient muscular dystrophy (MD). The misdiagnosis of toxoplasmosis was based on an increased IgG titre and muscle histopathology submitted to a local laboratory. Treatment for megaoesophagus included vertical feeding of wet food only, sildenafil and omeprazole. Dysphagia and regurgitation improved moderately. Presumptive hyperaesthesia and muscle pain were managed with anti-inflammatory doses of prednisolone. The patient was ultimately euthanased as a result of progressive MD signs and uraemia at 2 years of age. Relevance and novel information: This case report highlights the collective clinical features of MD, as they could be considered pathognomonic for this rare condition and must be differentiated from other myopathies via specific immunostaining of muscle biopsies. This is crucial to obtain a correct and early diagnosis, allowing instigation of potentially valuable treatments. Megaoesophagus is an inconsistent feature in feline MD in addition to the more commonly observed oropharyngeal dysphagia. Management with a canned diet, sildenafil, omeprazole and upright feeding was beneficial with moderate improvement in the frequency of regurgitation. Prednisolone was thought to minimise the presumptive myalgia.

Exonisation of an intronic L1 element in the dystrophin gene associated with X-linked muscular dystrophy in a Border Collie dog.

X-linked recessive dystrophinopathies are the most common muscular dystrophies (MDs) in humans and dogs. To date, 20 breed-specific MD-associated variants are described in the canine dystrophin gene (DMD), including one associated with dystrophin-deficient MD in the Border Collie mixed breed. Here, we report the diagnosis and follow-up of mild dystrophin-deficient MD in a 5-month-old male Border Collie, associated with a novel DMD variant. Diagnosis was based on neurological examination and laboratory evaluations including creatine kinase activity, electromyography and muscle biopsies with immunofluorescent staining. Inspection of the Sashimi plots of the RNA-seq data from the affected muscle biopsy led to the discovery of a 162-bp L1 pseudoexon in DMD intron 63, introducing a frameshift and a premature stop codon (NM_001003343.1: c.9271_9272insN[162] p.(Ala3091fs*21)). Reduced DMD mRNA levels were detected for both the non-pseudoexon (50× less) and pseudoexon (3× less) containing transcripts in the affected muscle, compared with the level of the non-pseudoexon containing transcript in a control muscle, resulting in very low dystrophin protein levels and the upregulation of utrophin. Because the variant was only found in the affected dog, not in the healthy mother and grandmother, or in 108 unrelated Border Collies from the Belgian population (46 males and 62 females), it was considered a de novo variant. Although the prognosis for dystrophinopathy is generally regarded as poor, the dog stabilised at the age of 6 months and is still clinically stable at the age of 2 years.

Advances in oligosaccharides and polysaccharides with different structures as wall materials for probiotics delivery: A review.

Probiotics are active microorganisms that are beneficial to the health of the host. However, probiotics are highly sensitive to the external environment, and are susceptible to a variety of factors that reduce their activity during production, storage, and use. Microencapsulation is an effective method that enhances probiotic activity. Macromolecules like polysaccharides, who classified as biologically active prebiotics, have attracted significant attention for their utility in probiotic microencapsulation. This article summarized the types of commonly used microencapsulation materials and their structural characteristics from the perspective of polysaccharides prebiotics. It also discussed recent advancements, probiotic-prebiotic microcapsule-based modulation of the immune system, as well as the associated limitations. Furthermore, the advantages and disadvantages of eight prebiotics as microencapsulation wall materials. The honeycomb structure of ß-glucan enhances the bioavailability of probiotics, while, fructooligosaccharide and galactooligosaccharides improve microbead structure to tightly encapsulate probiotics. The terminal reducing groups of isomaltooligosaccharides and the free hydroxyl groups in xylooligosaccharides also positively affect the structure of microcapsules. Prebiotics not only enhance the survival rate and biological activity of probiotics as embedding materials during storage, but also exert their own probiotic effects. Collectively, prebiotics holds great promise as microencapsulation materials for probiotics delivery.

Design, synthesis and biological evaluation of a novel PAK1 degrader for the treatment of triple negative breast cancer.

Triple-negative breast cancer is one of the most malignant subtypes in clinical practice, and it is urgent to find new therapies. The p21-activated kinase I (PAK1) has been considered to be an attractive therapeutic target for TNBC. In this study, we designed and synthesized a series of novel PROTAC PAK1 degraders by conjugating VHL or CRBN ligase ligands to PAK1 inhibitors which are connected by alkyl chains or PEG chains. The most promising compound, 19s, can significantly degrade PAK1 protein at concentrations as low as 0.1 µM, and achieves potent anti-proliferative activity with an IC50 value of 1.27 µM in MDA-MB-231 cells. Additionally, 19s exhibits potent anti-migration activity in vitro and induces rapid tumor regression in vivo. Collectively, these findings document that 19s is a potent and novel PAK1 degrader with promising potential for TNBC treatment.

Oligoasthenospermia is correlated with increased preeclampsia incidence in subfertile couples undergoing in vitro fertilization and embryo transfer: a secondary analysis of a randomized clinical trial.

OBJECTIVE: To evaluate whether intergroup differences in the risk of maternal pregnancy complications after in vitro fertilization (IVF) vary with male factor. DESIGN: A post hoc exploratory secondary analysis of data from a multicenter, randomized, controlled noninferiority trial (NCT03118141). SETTING: Academic fertility centers. PATIENT(S): A total of 1,131 subfertile women with complete recording of their male partner's semen parameters during the trial were enrolled. All participants underwent intracytoplasmic sperm injection followed by frozen embryo transfer (ET) as part of their assisted reproductive technology treatment protocol. INTERVENTION(S): Women were divided into the oligoasthenospermia (n = 405) and normospermia (n = 726) groups according to the quality of male sperm. MAIN OUTCOME MEASURE(S): Pregnancy complications, principally including the incidence of preeclampsia. RESULT(S): Notably, we found that the risk of maternal preeclampsia was significantly higher in the oligoasthenospermia group than in the normospermia group. After adjustments for confounding factors by multivariate logistic regression analysis, the incidence of preeclampsia in the oligoasthenospermia group was still significantly higher than that in the normospermia group (6.55% vs. 3.60%; odds ratio, 0.529; 95% confidence interval, 0.282-0.992). However, there were no significant differences in terms of embryo quality, cumulative live birth rate, other pregnancy complications, or neonatal outcomes between the 2 groups. CONCLUSION(S): Oligoasthenospermia was associated with a higher risk of maternal preeclampsia in subfertile couples undergoing IVF-ET treatment. In clinical practice, it is essential to thoroughly evaluate the sperm quality and quantity of male partners before IVF-ET. Further research is needed to establish the causal relationships between semen quality and adverse pregnancy complications, particularly preeclampsia, and explore potential interventions.

Polycyclic aromatic hydrocarbon and its adducts in peripheral blood: Gene and environment interaction among Chinese population.

BACKGROUND: Benzo(a)pyrene (B[a]P) is the most widely concerned polycyclic aromatic hydrocarbons (PAHs), which metabolizes benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE) in vivo to produce carcinogenic effect on the body. Currently, there is limited research on the role of the variation of metabolic enzymes in this process. METHODS: We carried out a study including 752 participants, measured the concentrations of 16 kinds PAHs in both particle and gaseous phases, urinary PAHs metabolites, leukocyte BPDE-DNA adduct and serum BPDE- Albumin (BPDE-Alb) adduct, and calculated daily intake dose (DID) to assess the cumulative exposure of PAHs. We conducted single nucleotide polymorphism sites (SNPs) of metabolic enzymes, explored the exposure-response relationship between the levels of exposure and BPDE adducts using multiple linear regression models. RESULT: Our results indicated that an interquartile range (IQR) increase in B[a]P, PAHs, BaPeq, 1-hydroxypyrene (1-OHP), 1-hydroxynaphthalene (1-OHNap) and 2-hydroxynaphthalene (2-OHNap) were associated with 26.53 %, 24.24 %, 28.15 %, 39.15 %, 12.85 % and 14.09 % increase in leukocyte BPDE-DNA adduct (all P < 0.05). However, there was no significant correlation between exposure with serum BPDE-Alb adduct (P > 0.05). Besides, we also found the polymorphism of CYP1A1(Gly45Asp), CYP2C9 (Ile359Leu), and UGT1A1(downstream) may affect BPDE adducts level. CONCLUSION: Our results indicated that leukocyte BPDE-DNA adduct could better reflect the exposure to PAHs. Furthermore, the polymorphism of CYP1A1, CYP2C9 and UGT1A1affected the content of BPDE adducts.

Mussel-inspired adhesive drug-loaded hydrogels for oral ulcers treatment.

Oral aphthous ulcers are common mucosal lesions that cause pain and discomfort. There are diverse biomaterials and drug treatments for oral ulcers used in both research and clinical settings. However, the complex oral environment often results in low adhesion and short drug retention times, which lead to poor drug availability and treatment outcomes. In this study, a mussel-inspired adhesive hydrogel was developed by grafting catechol onto hyaluronic acid (C-HA), and dopamine was added for oxidative pre-polymerization to form modified hyaluronic acid (M-HA), which remarkably increased the adhesion of the hydrogels. Then, M-HA was interpenetrated into the gelatin methacryloyl (GelMA) network. Chlorhexidine gluconate (CHG) was then incorporated into the hydrogel to enhance its availability and therapeutic effect through its sustained-release capability. The GelMA/M-HA hydrogel demonstrated strong adhesion to wet tissues, antibacterial and anti-inflammatory properties, and good biocompatibility. In both rat oral ulcers and infected wounds, the adhesive hydrogel significantly accelerated the healing of the ulcers and infected wounds. These results indicated that this adhesive hydrogel offers a promising new strategy for the treatment of oral ulcers in clinical practice. STATEMENT OF SIGNIFICANCE: Oral ulcers are a common and high-incidence mucosal condition that seriously affect people's daily lives, often making it difficult for patients to chew and speak. However, a dynamic oral environment with various types of bacteria influences drug availability and treatment effects in clinical settings. To address this challenge, an adhesive, mussel-inspired, drug-loaded hydrogel was constructed using natural macromolecules (hyaluronic acid and gelatin) with good biocompatibility. Chlorhexidine gluconate (CHG), with its broad-spectrum antibacterial activity, has been incorporated to synergistically promote oral ulcer healing. The splendid adhesion, antibacterial, and therapeutic effects of this hydrogel demonstrated a new strategy for treating oral ulcers.

The Contribution of Noun and Verb Lexicon Sizes to Later Grammatical Outcomes in Mandarin-Speaking Children With Cochlear Implants.

PURPOSE: The present study evaluated the applicability of the sentence-focused framework to Mandarin-speaking children with cochlear implants (CIs) by examining the relative contribution of receptive/expressive noun and verb lexicon sizes to later grammatical complexity. METHOD: Participants were 51 Mandarin-speaking children who received cochlear implantation before 30 months of age. At 12 months after CI activation, parents were asked to endorse words that their child could understand only or understand and say using the infant version of the Early Vocabulary Inventory. At 24 months after CI activation, parents were asked to endorse the grammatical structures that their children were able to say using the Grammatical Complexity subtest in the Mandarin Communicative Development Inventory-Taiwan. Children's receptive/expressive noun and verb lexicon sizes and grammatical complexity scores were computed from these parent checklists. RESULTS: Correlational analyses showed that children's receptive/expressive noun and verb lexicon sizes at 12 months after CI activation were all highly correlated with their grammatical complexity scores at 24 months after CI activation (ρs = .52-.63, ps < .001). Regression analyses further revealed that verb lexicon sizes at 12 months after CI activation outweighed noun lexicon sizes in accounting for grammatical complexity at 24 months after CI activation. CONCLUSIONS: Our findings supported the prediction of the sentence-focused framework. Emphasizing the role of verbs in early intervention has the potential to enhance grammatical outcomes in Mandarin-speaking children with CIs. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.26129044.

Prognostic significance of hemoglobin, albumin, lymphocyte, and platelet (HALP) score in breast cancer: a propensity score-matching study.

BACKGROUND: The hemoglobin-albumin-lymphocyte-platelet (HALP) score functions as a comprehensive index that assesses the systemic inflammatory response, nutritional, and immune status. This study aimed to explore the relationship between preoperative HALP score and the prognosis of BC patients and to develop predictive nomograms. METHODS: Clinicopathological data were collected for BC patients who underwent mastectomy between December 2010 and April 2014 from Sun Yat-sen University Cancer Center. The optimal cutoff value for HALP was determined by maximally selected rank statistics for overall survival data. Propensity score matching (PSM) was applied to develop comparable cohorts of high-HALP group and low-HALP group. Kaplan-Meier curves and Cox regression analyses were performed to determine the impact of HALP on BC patients. Prognostic nomograms were developed based on the multivariate Cox regression method. Then, the concordance index (C-index), calibration plots, and decision curves analysis (DCA) were applied to evaluate the prognostic performance of the nomograms. RESULTS: A total of 1,856 patients were included as the primary cohort, and 1,470 patients were matched and considered as the PSM cohort. In the primary cohort, the 5-year overall survival (OS) and progression-free survival (PFS) rates for high-HALP group (≥ 47.89) and low-HALP group (< 47.89) were 94.4% vs. 91.0% (P = 0.005) and 87.8% vs. 82.1% (P = 0.005), respectively. Similar results were observed in PSM cohort (5-year OS, 94.3% vs. 90.8%, P = 0.015; 5-year PFS, 87.5% vs. 83.2%, P = 0.036). Notably, multivariate Cox regression analysis in the PSM cohort showed that HALP could independently predict BC patient prognosis in both OS (HR: 0.596, 95%CI [0.405-0.875], P = 0.008) and PFS (HR: 0.707, 95%CI [0.538-0.930], P = 0.013). OS and PFS nomograms showed excellent predictive performance with the C-indexes of 0.783 and 0.720, respectively. The calibration plots and DCA also indicated the good predictability of the nomograms. Finally, subgroup analysis further demonstrated a favorable impact of HALP on both OS and PFS. CONCLUSION: Preoperative HALP score can be used as a reliable independent predictor of OS and PFS in BC patients, and the nomograms may provide a personalized treatment strategy.