Deep learning-guided adjuvant chemotherapy selection for elderly patients with breast cancer.

PURPOSE: The efficacy of adjuvant chemotherapy in elderly breast cancer patients is currently controversial. This study aims to provide personalized adjuvant chemotherapy recommendations using deep learning (DL). METHODS: Six models with various causal inference approaches were trained to make individualized chemotherapy recommendations. Patients who received actual treatment recommended by DL models were compared with those who did not. Inverse probability treatment weighting (IPTW) was used to reduce bias. Linear regression, IPTW-adjusted risk difference (RD), and SurvSHAP(t) were used to interpret the best model. RESULTS: A total of 5352 elderly breast cancer patients were included. The median (interquartile range) follow-up time was 52 (30-80) months. Among all models, the balanced individual treatment effect for survival data (BITES) performed best. Treatment according to following BITES recommendations was associated with survival benefit, with a multivariate hazard ratio (HR) of 0.78 (95% confidence interval (CI): 0.64-0.94), IPTW-adjusted HR of 0.74 (95% CI: 0.59-0.93), RD of 12.40% (95% CI: 8.01-16.90%), IPTW-adjusted RD of 11.50% (95% CI: 7.16-15.80%), difference in restricted mean survival time (dRMST) of 12.44 (95% CI: 8.28-16.60) months, IPTW-adjusted dRMST of 7.81 (95% CI: 2.93-11.93) months, and p value of the IPTW-adjusted Log-rank test of 0.033. By interpreting BITES, the debiased impact of patient characteristics on adjuvant chemotherapy was quantified, which mainly included breast cancer subtype, tumor size, number of positive lymph nodes, TNM stages, histological grades, and surgical type. CONCLUSION: Our results emphasize the potential of DL models in guiding adjuvant chemotherapy decisions for elderly breast cancer patients.

Ultrastable Anti-Acid "Shield" in Layered Silver Coordination Polymers.

Surface passivation technology provides noble-metal materials with limited chemical stability, especially under highly acidic condition. To design effective strategy to enhance stability of noble-metal particles, an understanding of their surface anticorrosion mechanism at the atomic level is desirable by using two-dimensional (2D) noble-metal coordination polymer (CP) as an ideal model for their interfacial region. With the protection of 2-thiobenzimidazole (TBI), we isolated two Ag-based 2D CPs, {Ag14 (TBI)12 X2 }n (S-X, where S denotes sheet and X=Cl or Br). These compounds exhibited excellent chemical stability upon immersion in various common solvents, boiling water, boiling ethanol, 10 % hydrogen peroxide, concentrated acid (12 M HCl), and concentrated alkali (19 M NaOH). Systematic characterization and DFT analyses demonstrate that the superior stability of S-X was attributed to the hydrophobic organic shell and dynamic proton buffer layer acting as a double protective "shield".

A Direction-of-Arrival Estimation Algorithm Based on Compressed Sensing and Density-Based Spatial Clustering and Its Application in Signal Processing of MEMS Vector Hydrophone.

Direction of arrival (DOA) estimation has always been a hot topic for researchers. The complex and changeable environment makes it very challenging to estimate the DOA in a small snapshot and strong noise environment. The direction-of-arrival estimation method based on compressed sensing (CS) is a new method proposed in recent years. It has received widespread attention because it can realize the direction-of-arrival estimation under small snapshots. However, this method will cause serious distortion in a strong noise environment. To solve this problem, this paper proposes a DOA estimation algorithm based on the principle of CS and density-based spatial clustering (DBSCAN). First of all, in order to make the estimation accuracy higher, this paper selects a signal reconstruction strategy based on the basis pursuit de-noising (BPDN). In response to the challenge of the selection of regularization parameters in this strategy, the power spectrum entropy is proposed to characterize the noise intensity of the signal, so as to provide reasonable suggestions for the selection of regularization parameters; Then, this paper finds out that the DOA estimation based on the principle of CS will get a denser estimation near the real angle under the condition of small snapshots through analysis, so it is proposed to use a DBSCAN method to process the above data to obtain the final DOA estimate; Finally, calculate the cluster center value of each cluster, the number of clusters is the number of signal sources, and the cluster center value is the final DOA estimate. The proposed method is applied to the simulation experiment and the micro electro mechanical system (MEMS) vector hydrophone lake test experiment, and they are proved that the proposed method can obtain good results of DOA estimation under the conditions of small snapshots and low signal-to-noise ratio (SNR).

A case report of an intermediate phenotype between congenital myasthenic syndrome and D-2- and L-2-hydroxyglutaric aciduria due to novel SLC25A1 variants.

BACKGROUND: Variants in the SLC25A1 gene are associated with a severe neurometabolic disease, D-2- and L-2-hydroxyglutaric aciduria (D/L-2-HGA). A report in 2014 presented the first account of congenital myasthenic syndrome (CMS) with mild intellectual disability (ID) caused by SLC25A1. To date, only two missense variants in SLC25A1 have been linked to CMS. CASE PRESENTATIONS: A Chinese boy presented fatigable muscular weakness, myasthenic crisis, epilepsy and developmental delay along with mild elevation of urinary 2-ketoglutarate (2-KG) and lactic acid levels. He showed a partial response to pyridostigmine. Genetic analysis using trio whole-exome sequencing (WES), Sanger sequencing, and cosegregation analyses revealed two novel pathogenic variants of SLC25A1 (c.628C > T, p.R210X; c.145G > A, p.V49M). CONCLUSIONS: We report a boy who carries novel compound heterozygous variants of SLC25A1 and presents a phenotype intermediate between CMS and D/L-2-HGA. This case expands the range of known phenotypes and genotypes associated with SLC25A1.

Developmental Regression and Epilepsy of Infancy with Migrating Focal Seizures Caused by TBCD Mutation: A Case Report and Review of the Literature.

Microtubule dynamics plays a crucial role in neuronal development and function. Variants in the tubulin cofactor D (TBCD) gene, which encodes one of the five co-chaperones required for assembly and disassembly of α/ß-tubulin heterodimers, may lead to neurodevelopmental disorders. We aimed to study the clinical, electroencephalographic, and imaging features of a male patient with TBCD variants, and to provide a detailed review of the previously reported cases of TBCD-related neurological disorders. The patient presented with early-onset developmental regression, secondary microcephaly, epilepsy of infancy with migrating focal seizures, hypotonia, and brain atrophy with thin corpus callosum on brain magnetic resonance imaging. Genetic analyses of the family members revealed a compound heterozygous variant of c.230A > G (p.H77R) in the proband and deletion of exons 28 to 39 of TBCD, which has not been previously reported and was inherited from his carrier parents. Epilepsy of the patient was refractory to numerous antiepileptic drugs. The review of 33 previously reported patients revealed that the age at the onset was very early, and all the patients had presentations during the first year of life. This case report provides insight regarding the clinical features and genetic etiology of TBCD-related tubulinopathy. Identification of phenotypes and genotypes in patients may help in early diagnosis and appropriate genetic counseling.

Clinical features of patients with paroxysmal kinesigenic dyskinesia, mutation screening of PRRT2 and the effects of morning draughts of oxcarbazepine.

BACKGROUND: The objective of this study was to summarize clinical features and PRRT2 mutations of paediatric paroxysmal kinesigenic dyskinesia (PKD) patients and observe the tolerability and effects of morning draughts of oxcarbazepine. METHODS: Twenty patients diagnosed with PKD at Children's Hospital of Fudan University between January 2011 and December 2015 were enrolled. These patients' medical records were reviewed. Peripheral venous blood was obtained from all enrolled patients, and polymerase chain reaction (PCR) and Sanger sequencing were used to sequence proline-rich transmembrane protein 2 (PRRT2) gene mutations. Clinical features of PKD patients with and without PRRT2 mutations were compared. All enrolled patients were treated with morning draughts of oxcarbazepine (OXC). The starting dose was 5 mg/kg·d, and the dose was increased by 5 mg/kg·d each week until attacks stopped. Effective doses and adverse effects were recorded. RESULTS: For all enrolled patients, dyskinesia was triggered by sudden movement. Dyskinetic movement usually involved the limbs and was bilateral; the majority of enrolled patients exhibited both dystonia and choreoathetosis. We identified PRRT2 mutations in 5 patients, including 4 familial patients and 1 sporadic patient. All 20 patients took low doses of OXC (5-20 mg/kg·d) as draughts in the morning, and dyskinesia attacks stopped in 19 patients. CONCLUSIONS: Paediatric PKD patients have various phenotypes. PRRT2 mutations are common in familial cases. OXC taken as morning draughts can be a treatment option for paediatric PKD patients.

MEMS Hydrophone Signal Denoising and Baseline Drift Removal Algorithm Based on Parameter-Optimized Variational Mode Decomposition and Correlation Coefficient.

Underwater acoustic technology is an important means of detecting the ocean. Due to the complex influence of the marine environment, there is a lot of noise and baseline drift in the signals collected by hydrophones. In order to solve this problem, this paper proposes a denoising and baseline drift removal algorithm for MEMS vector hydrophone based on whale-optimized variational mode decomposition (VMD) and correlation coefficient (CC). Firstly, the power spectrum entropy (PSE), which reflects the variation characteristics of the signal frequency is selected as the fitness function of the whale-optimization algorithm to find the parameters (K,α) of the VMD. It is easier to find the global optimal solution of the parameters by combining the whale-optimization algorithm. Then, using the VMD algorithm after obtaining the parameters, the original signal is decomposed to obtain the intrinsic mode functions (IMFs), and calculating the correlation coefficients (CCs) between the IMFs and the original signal. Finally, the CC threshold is used to remove the noise IMFs, and the rest of the useful IMFs are reconstructed to complete the denoising and baseline drift removal process of the original signals. In the simulation experiments, the algorithm proposed in this paper shows better performance by comparing conventional digital signal-processing methods and the related algorithms proposed recently. Applied in the experiments of a MEMS hydrophone, the effectiveness of the proposed algorithm is also verified. This algorithm can provide new ideas for signal denoising and baseline drift removal.

PTENp1, a natural sponge of miR-21, mediates PTEN expression to inhibit the proliferation of oral squamous cell carcinoma.

PTENp1, non-coding RNA (ncRNA) pseudogene, is involved in oral squamous cell carcinoma (OSCC). The precise effects mediated by PTENp1 transcripts within intricate regulatory networks involving molecular interactions with ancestral gene PTEN and tumorigenicity in OSCC remain unclear. Here, we found that PTENp1 was aberrantly expressed in OSCC. There was a positive correlation between the expression levels of PTENp1 and PTEN. Further, we showed that PTENp1 acted as a competing endogenous RNA that protects PTEN transcripts from being inhibited by miR-21, and consequently inhibited proliferation and colony formation and triggered S-G2/M cell cycle arrest through the AKT pathway. Also, the homogeneous relationship between expression of PTENp1 and PTEN was confirmed in OSCC tumor xenografts. Finally, low expression of PTENp1 and PTEN was negatively associated with histological differentiation and OSCC prognosis. The present work provided the first evidence for the extraordinary crosstalk among PTENp1, PTEN, and miR-21, and rendered a new light on the treatment of OSCC. © 2016 Wiley Periodicals, Inc.

Low-dose propranolol for infantile hemangioma of the head and neck: Analysis of 23 consecutive patients.

BACKGROUND: More and more infantile hemangiomas (IH) are being treated with propranolol, but the effectiveness, dosage, and treatment course are still in dispute. The aim of this observational study was to describe the therapeutic response, tolerance, and safety of low-dose propranolol in 23 children with IH of the head and neck. METHODS: Data were collected from the medical charts of patients treated with low-dose propranolol from December 2009 through November 2011. Oral dose was 1-1.5 mg/kg once per day. Blood pressure and heart rate were monitored during the first 24 h of treatment. In the absence of side-effects, treatment was continued at home and the child was re-evaluated every month. RESULTS: All patients had a good response, even if treated with corticosteroid previously. Color and growth changes within 1 week were noted. Treatment continued for a mean total duration of 6 months until the IH had totally disappeared or stabilized. There were no severe adverse reactions. Side-effects were limited and mild, including blood pressure decrease, somnolence, and nausea. No relapse was noted. CONCLUSIONS: Low-dose propranolol appears to be effective and safe for IH, especially for those patients previously treated with corticosteroid and who had no response or severe side-effects.

Six-month efficacy of the Ketogenic diet is predicted after 3 months and is unrelated to clinical variables.

OBJECTIVE: The aim of this study was to evaluate the 6-month efficacy of a Ketogenic diet (KD) in children with drug-resistant epilepsy and to analyze the associated factors that affect the efficacy of a KD. METHODS: Eighty-seven pediatric patients with drug-resistant epilepsy who followed a KD for at least 6 months were included in this study. The efficacy of a KD was assessed based upon the seizure frequency, as recorded by parents and caregivers. The number of cases and the degree of efficacy in different age ranges were also considered. The effects of gender, age, seizure type, etiology, blood glucose and ketone levels, seizure frequency before the diet, and cognition on the length of time on a KD were analyzed. RESULTS: (1) There was no significant correlation between the length of time on a KD and efficacy (χ(2)=2.31, P=0.51). The 3-month efficacy of a KD was 51%, which did not further increase when the course was extended to 6 months. (2) There was a positive correlation between increased cognition and the efficacy of a KD after 3 months (γ=0.31, P=0.003). (3) The efficacy analysis of 3-month treatment with a KD revealed, with respect to seizure types, that there were 37 patients with multiple seizure phenotypes and 50 patients with a single seizure phenotype. The overall efficacy of a KD in the group with multiple seizure phenotypes was 61%. The efficacy of a KD was not statistically associated with a coexisting syndrome or a type of syndrome; however, the efficacy of a KD had a tendency to be increased in certain types of syndromes. The overall efficacy in the group with a single seizure phenotype was 87%, and the efficacy was not associated with seizure type. (4) The 3-month efficacy of a KD was not correlated with age, gender, etiology, blood glucose or ketone levels, or the seizure frequency before treatment. CONCLUSION: An observation time of 3 months is appropriate for assessing the efficacy of a KD in treating children with drug-resistant epilepsy. The factors that likely influence the efficacy of a KD are unclear, but our study suggests that incorporating more patient samples will help determine whether patients with certain syndromes can benefit from a KD.

[Treatments of stage-Is testicular mixed germ cell tumors: A report of 3 cases].

OBJECTIVE: To investigate different treatment methods for stage-Is testicular mixed germ cell tumors (TMGCTs). METHODS: We retrospectively analyzed the clinical data about 3'cases of stage-Is TMGCTs (aged 26-39 years) treated in the 175th Hospital of PLA, reviewed relevant literature, and explored the clinical characteristics of TMGCTs. RESULTS: Of the 3 patients, 1 was treated by radical orchiectomy, 1 by radical orchiectomy + retroperitoneal lymph node dissection + BEP chemotherapy scheme, and the other by radical orchiectomy + radiotherapy. The pathological components of TMGCTs were immature teratoma, seminoma, spermatocytoma, chorioepithelioma, embryonal carcinoma, and yolk sac tumor. No recurrence or distant metastasis was found during the 24-month follow-up after surgery. CONCLUSION: The diagnosis of TMGCTs primarily depends on physical examination, ultrasonography, MRI, and measurement of serum tumor markers, while its confirmation necessitates pathological examination, and its treatment is basically radical orchiectomy.

Circulating microRNA-21 (MIR-21) and phosphatase and tensin homolog (PTEN) are promising novel biomarkers for detection of oral squamous cell carcinoma.

The purpose of this study was to investigate the potential of the blood levels of MIR-21 and PTEN as novel biomarkers for oral squamous cell carcinoma (OSCC). We initially detected MIR-21 and PTEN using real-time RT-PCR from 90 blood samples and then compared their results with expression in cancer tissues from 10 OSCC patients. Finally, we examined the relationship between these markers and clinical parameters. Blood MIR-21 and PTEN had significant diagnostic value for OSCC and, to an extent, correlated with the expression level of tumour MIR-21 and PTEN. In addition, they were associated with differentiation and nodal status. Thus circulating MIR-21 and PTEN might represent new complementary tumour markers for OSCC.

Surgical management of squamous cell carcinoma of the lower lip: an experience of 109 cases.

OBJECTIVE: We are presenting our experience collected from a series of 109 cases with SCC of the lower lip focusing on clinical features of patients and surgical approach. STUDY DESIGN: We retrospectively analyzed medical records of patients diagnosed with Squamous Cell Carcinoma (SCC) of the lower lip at the Oral and Maxillofacial surgery at Xi'an Jiaotong University during a period between 1999 and 2008. RESULTS: A total of 109 patients with lip cancer were included in the study. When no frozen-section test was performed, the neoplasia was removed with a margin of at least 6 mm. Different surgical techniques were used for lip reconstruction after tumor excision. Neck dissection was performed in all patients with clinically palpable lymph nodes. Median follow-up was 38 months. During follow-up, recurrence occurred in 5 patients, 3 patients developed neck metastases, distant metastases developed in 1 patient. Five patients died during observation period. CONCLUSIONS: The patient-related and defect-related issues must be taken into consideration during reconstruction for surgical defect. For N0 patients, we recommend wait-and-see policy. Early detection, careful follow-up and prompt neck is essential for the successful treatment.

Etiologies and clinical characteristics of acute ataxia in a single national children's medical center.

OBJECTIVE: To analyze etiologic factors of pediatric acute ataxia and to identify the severity of its underlying causes for urgent medical intervention. METHODS: Clinical data of children diagnosed with acute ataxia between December 2015 and December 2021 from one national medical center were analyzed retrospectively. RESULTS: A total of 99 children (59 boys, 40 girls), median age at disease onset 55 (range: 12-168) months, were enrolled. The median follow period was 46 (range 6-78) months. Eighty-six (86.9 %) children were diagnosed with immune-associated acute ataxia, among which acute post-infectious cerebellar ataxia (APCA) was the most common diagnosis (50.5 %), followed by demyelinating diseases of the central nervous system (18.2 %) and Guillain-Barré syndrome (9.1 %). On cerebrospinal fluid (CSF) examination, 35/73 (47.9 %) patients had pleocytosis (>5 cells/mm3), and 18/73 (24.7 %) had elevated protein levels. Thirty-one patients (31.3 %) had an abnormal cerebral MRI. Children with other immune-associated acute cerebellar ataxia had more extracerebellar symptoms, intracranial MRI lesions, abnormal CSF results, longer hospital stay, higher recurrence rates and incidence of neurological sequelae than children with APCA. CONCLUSION: Immune-associated acute ataxia is the main cause of pediatric acute ataxia, among which APCA is the most common phenotype. However, some immune-associated diseases, especially autoantibody-mediated disease, which has a higher recurrence rate and neurological sequelae account for an increasing proportion of pediatric acute ataxia. When children present with extracerebellar symptoms, abnormal cranial MRI or CSF results, and without prodromal infection, prudent differential diagnosis is recommended.

Clinical analysis of developmental and/or epileptic encephalopathy with spike-and-wave activation in sleep: A single tertiary care center experience in China.

PURPOSE: To analyze the electroclinical features of patients with developmental and/or epileptic encephalopathy with spike-and-wave activation in sleep (DEE/EE-SWAS) and study the efficacy of different therapies on seizure control, electroencephalogram (EEG) improvements of electrical status epilepticus during sleep (ESES), and cognition outcomes. METHODS: Patients with DEE/EE-SWAS who underwent at least one follow-up EEG 3 months after therapy were retrospectively enrolled. The demographic and clinical characteristics of the patients were analyzed. Variables that influenced the outcomes were evaluated using logistic regression models. RESULTS: In total, 87 patients (47 males) were included. The median age at ESES recognition was 81.0 months (IQR 64.0, 96.0). Forty-six patients were diagnosed with self-limited focal epilepsies (SeLFEs) before ESES recognition, 24 with developmental and epileptic encephalopathies with spike-and-wave activation in sleep (DEE-SWAS), and 17 with other epilepsies. Steroids, benzodiazepines, and antiseizure medications (ASMs) were the initial treatment options for ESES. Patients with structural etiologies or slow EEG backgrounds at the time of ESES recognition were less likely to respond to treatment than other patients. However, only children with slow EEG backgrounds had lower odds of response in logistic regression models. Children with clinical or EEG response showed improvements in cognition. CONCLUSION: Steroids, benzodiazepines, and ASMs are effective treatments for patients with DEE/EE-SWAS. Children with structural etiologies or slow EEG backgrounds at the time of ESES recognition may have a poor long-term prognosis. The efficacy of seizure reduction and EEG improvement is associated with cognitive improvement.

Highly intense NIR emissive Cu4Pt2 bimetallic clusters featuring Pt(i)-Cu4-Pt(i) sandwich kernel.

Metal nanoclusters (NCs) capable of near-infrared (NIR) photoluminescence (PL) are gaining increasing interest for their potential applications in bioimaging, cell labelling, and phototherapy. However, the limited quantum yield (QY) of NIR emission in metal NCs, especially those emitting beyond 800 nm, hinders their widespread applications. Herein, we present a bright NIR luminescence (PLQY up to 36.7%, ∼830 nm) bimetallic Cu4Pt2 NC, [Cu4Pt2(MeO-C6H5-C[triple bond, length as m-dash]C)4(dppy)4]2+ (dppy = diphenyl-2-pyridylphosphine), with a high yield (up to 67%). Furthermore, by modifying the electronic effects of R in RC[triple bond, length as m-dash]C- (R = MeO-C6H5, F-C6H5, CF3-C6H5, Nap, and Biph), we can effectively modulate phosphorescence properties, including the PLQY, emission wavelength, and excited state decay lifetime. Experimental and computational studies both demonstrate that in addition to the electron effects of substituents, ligand modification enhances luminescence intensity by suppressing non-radiation transitions through intramolecular interactions. Simultaneously, it allows the adjustment of emitting wavelengths by tuning the energy gaps and first excited triplet states through intermolecular interactions of ligand substituents. This study provides a foundation for rational design of the atomic-structures of alloy metal NCs to enhance their PLQY and tailor the PL wavelength of NIR emission.

Determining individual suitability for neoadjuvant systemic therapy in breast cancer patients through deep learning.

BACKGROUND: The survival advantage of neoadjuvant systemic therapy (NST) for breast cancer patients remains controversial, especially when considering the heterogeneous characteristics of individual patients. OBJECTIVE: To discern the variability in responses to breast cancer treatment at the individual level and propose personalized treatment recommendations utilizing deep learning (DL). METHODS: Six models were developed to offer individualized treatment suggestions. Outcomes for patients whose actual treatments aligned with model recommendations were compared to those whose did not. The influence of certain baseline features of patients on NST selection was visualized and quantified by multivariate logistic regression and Poisson regression analyses. RESULTS: Our study included 94,487 female breast cancer patients. The Balanced Individual Treatment Effect for Survival data (BITES) model outperformed other models in performance, showing a statistically significant protective effect with inverse probability treatment weighting (IPTW)-adjusted baseline features [IPTW-adjusted hazard ratio: 0.51, 95% confidence interval (CI), 0.41-0.64; IPTW-adjusted risk difference: 21.46, 95% CI 18.90-24.01; IPTW-adjusted difference in restricted mean survival time: 21.51, 95% CI 19.37-23.80]. Adherence to BITES recommendations is associated with reduced breast cancer mortality and fewer adverse effects. BITES suggests that patients with TNM stage IIB, IIIB, triple-negative subtype, a higher number of positive axillary lymph nodes, and larger tumors are most likely to benefit from NST. CONCLUSIONS: Our results demonstrated the potential of BITES to aid in clinical treatment decisions and offer quantitative treatment insights. In our further research, these models should be validated in clinical settings and additional patient features as well as outcome measures should be studied in depth.

Personalized surgical recommendations and quantitative therapeutic insights for patients with metastatic breast cancer: Insights from deep learning.

Background: The role of surgery in metastatic breast cancer (MBC) is currently controversial. Several novel statistical and deep learning (DL) methods promise to infer the suitability of surgery at the individual level. Objective: The objective of this study was to identify the most applicable DL model for determining patients with MBC who could benefit from surgery and the type of surgery required. Methods: We introduced the deep survival regression with mixture effects (DSME), a semi-parametric DL model integrating three causal inference methods. Six models were trained to make individualized treatment recommendations. Patients who received treatments in line with the DL models' recommendations were compared with those who underwent treatments divergent from the recommendations. Inverse probability weighting (IPW) was used to minimize bias. The effects of various features on surgery selection were visualized and quantified using multivariate linear regression and causal inference. Results: In total, 5269 female patients with MBC were included. DSME was an independent protective factor, outperforming other models in recommending surgery (IPW-adjusted hazard ratio [HR] = 0.39, 95% confidence interval [CI]: 0.19-0.78) and type of surgery (IPW-adjusted HR = 0.66, 95% CI: 0.48-0.93). DSME was superior to other models and traditional guidelines, suggesting a higher proportion of patients benefiting from surgery, especially breast-conserving surgery. The debiased effect of patient characteristics, including age, tumor size, metastatic sites, lymph node status, and breast cancer subtypes, on surgery decision was also quantified. Conclusions: Our findings suggested that DSME could effectively identify patients with MBC likely to benefit from surgery and the specific type of surgery needed. This method can facilitate the development of efficient, reliable treatment recommendation systems and provide quantifiable evidence for decision-making.

Long-term efficacy and safety of tacrolimus in young children with myasthenia gravis.

OBJECTIVE: This study was performed to evaluate the efficacy and long-term safety of tacrolimus for young children with myasthenia gravis (MG). METHODS: Children with corticosteroids (CSs)-ineffective, CSs-dependent or CSs-intolerable MG treated with tacrolimus for at least one year were recruited. The Myasthenia Gravis Foundation of America (MGFA) clinical classification and MGFA post-intervention status (MGFA-PIS) were used to evaluate before tacrolimus administration and at the last visit, respectively. MG Activities of Daily Living (MG-ADL) score and the dose of prednisone were recorded. Patients were divided into responders and poor responders based on changes in MG-ADL score to investigate the factors that affected tacrolimus efficacy. Unfavorable events were recorded. RESULTS: Twenty-one patients with MG were enrolled. The median age of starting tacrolimus was 8.7 (range 2.2-15.1) years old. At the last visit, 15 patients (71.4%) achieved minimal manifestation (MM) or better status. The symptoms evaluated by MG-ADL improved significantly one month after initiating tacrolimus (p＜0.05) and the dose of prednisone decreased significantly three months later (p＜0.05), and it continued to improve throughout the study. Thirteen patients (61.9%) were ultimately weaned off prednisone. Compared with 16 responders, 5 poor responders had lower MG-ADL scores. MG-ADL score was the only clinical factor of tacrolimus efficacy. Intraocular pressure and transient urine microprotein were present in one patient. CONCLUSION: A course of tacrolimus of more than one year was effective and well-tolerated in young children with MG, and tacrolimus improved MG symptoms and reduced the dose and adverse events of oral prednisone.

The role of PDIA3 in oral squamous cell carcinoma and its value as A diagnostic and prognostic biomarker.

Background: This study aimed to investigate the role of protein disulfide isomerase A3 (PDIA3) in oral squamous cell carcinoma (OSCC) and evaluate its significance as a diagnostic and prognostic biomarker. Methods: Comprehensive bioinformatics analysis of the OSCC dataset from The Cancer Genome Atlas (TCGA) was performed. PDIA3 was depleted in CAL27 and SCC25 OSCC cells by transfection with PDIA3-specific siRNA oligos. The effects of PDIA3 downregulation on cell viability, apoptosis, and cell migration were evaluated using CCK8, ELISA, and wound healing assays, respectively. Results: The mRNA and protein expression of PDIA3 was significantly up-regulated in OSCC tissues compared to adjacent normal tissues. Knockdown of PDIA3 led to significantly decreased cell viability, increased apoptosis, and suppressed migratory ability in OSCC cells. The Kaplan-Meier survival curve showed that patients with higher PDIA3 expression levels had shorter survival than those with low PDIA3 levels. The receiver operating characteristic (ROC) curve indicated that PDIA3 had high sensitivity and accuracy for detecting OSCC (area under the curve (AUC): 0.917, CI: 0.879-0.955). Univariate and multivariate Cox regression analyses identified PDIA3 as an independent prognostic factor of OSCC. Furthermore, the depletion of PDIA3 inhibited AKT activity in OSCC cells. Gene set enrichment analysis (GSEA) indicated that PDIA3 is involved in various important biological functions and signaling pathways closely related to cancer development. Conclusion: PDIA3 plays an oncogenic role in OSCC and represents a good candidate as a diagnostic and prognostic biomarker for OSCC.