Rank Test Research Articles

Clinical effect of the modified pharyngeal flap of bilateral muscular rings in the treatment of moderate and severe velopharyngeal insufficiency

To introduce the modified pharyngeal flap of bilateral muscular rings (BMR), and to discuss the clinical effect of this operation in the correction of moderate and severe velopharyngeal insufficiency. The clinical data of 18 patients who underwent BMR surgery in the Department of Craniofacial Plastic and Aesthetic Surgery, School of Stomatology, The Fourth Military Medical University from May 2019 to July 2021 were retrospectively analyzed. There were 10 males and 8 females, with a median age of 8.5 years (aged from 5 to 34 years). The patients were diagnosed preoperatively with moderate to severe velopharyngeal insufficiency (velopharyngeal closure ratio<0.7). The results of nasopharyngoscopy and speech assessment were compared and analyzed before operation and at the follow-up 6 months after the operation to evaluate the changes in velopharyngeal function and speech. Eighteen patients underwent BMR, 4 patients had snoring (the symptom disappeared after a few weeks in 3 cases), and 2 patients had local erosion of the wound, which delayed healing. Postoperative nasopharyngoscopy showed that all patients achieved comparatively complete velopharyngeal closure, some patients got enhanced lateral pharyngeal wall motility, and all patients got active motility of posterior pharyngeal wall flap. The postoperative speech assessment was significantly improved compared with that before the operation. The preoperative median score was 9 (range 7-12), and the postoperative median score was 2 (range 0-4). The statistical analysis was performed by paired non-parametric Wilcoxon signed rank test, and the difference was statistically significant (P<0.001). BMR is a reliable method for the treatment of moderate and severe velopharyngeal insufficiency. This technique can achieve functional contraction of the full circumference of the ventilator while preserving the obstructive effect of the posterior pharyngeal wall flap, which is helpful to balance nasal ventilation and velopharyngeal closure and improve the velopharyngeal function of patients.

Drawing a line from CO2 emissions to health—evaluation of medical students’ knowledge and attitudes towards climate change and health following a novel serious game: a mixed-methods study

BackgroundEducation is urgently needed to equip medical students with knowledge, values and skills to promote planetary health. However, the current literature offers little insight into evidence-based approaches and best practices. In response to this pressing need, a novel serious game was introduced into the medical curriculum at Erasmus Medical Center in 2023. The aim of this study was to evaluate the knowledge and attitudes of medical students after they had played a serious game that addresses climate change and health.MethodsIn accordance with a mixed-methods design, quantitative data were collected using pre- and post-intervention surveys. Differences were assessed using the Wilcoxon signed rank test. Focus group discussions were held after the game and thematically analysed.ResultsOne hundred forty-five students (38.6% of the entire cohort) played the game, of which 59 students completed the pre- and post-intervention surveys. After the game, self-reported knowledge increased. Regarding objective knowledge, an increase in the proportion of students who answered one of the two questions correctly was observed, while the proportion of correct responses decreased for the other question. Student’s responses to two out of five attitude questions were significantly more positive. The proportion of students who recognized the importance of climate change education, to inform patients and society about the health impacts of climate change, increased. Moreover, survey results indicated a significant increase in climate worry subsequent to the game. Eleven students participated in the focus group discussions. Thematic analysis highlighted participants’ reflections on the roles and responsibilities in climate change and health, along with their realisation of the tools for action that climate and health co-benefits provide. Another significant aspect was the importance participants placed on learning alongside peers with diverse attitudes. Additionally, participants appreciated the tangible overview of climate change and health provided by the serious game.ConclusionsOur novel serious game addressed an important gap in the medical curriculum. The game can enable medical students to cultivate the necessary knowledge and attitudes to promote health in times of a climate crisis. The accompanying climate worry needs attention through the empowerment of students’ agency to foster change.

Comparison Analysis of Financial Performance and Financial Distress before and during the Covid-19 Pandemic

The purpose study was to analyze a comparison of financial performance and financial distress before and during the Covid-19 pandemic in the Hotel, Restaurant, and Tourism sub-sector companies listed on the Indonesia Stock Exchange for the 2018-2021 period. In this study, a comparative descriptive method was used with a quantitative approach to test the impact of Covid-19 on financial performance and financial distress. The final sample of this study was 19 companies based on the elimination of the criteria that were only needed in this study. The proxies used to measure financial performance are profitability ratios (ROA, ROE, and NPM), while financial distress uses the Altman Z-Score model. Furthermore, these ratios were tested with a different test using the Wilcoxon sign rank test. The results showed that there were significant differences in the ratios of financial performance which included ROA, ROE, and NPM. Meanwhile, financial distress (Z-Score) also experienced significant differences between before and during the Covid-19 pandemic.

Fibrinogen-albumin ratio predicts treatment response in phospholipase A2 receptor-associated membranous nephropathy with nephrotic syndrome

Background The M-type phospholipase A2 receptor (PLA2R)-associated primary membranous nephropathy (PMN) is an immune-related disease in adults with increasing morbidity and variable treatment response, in which inflammation may contribute to the multifactorial immunopathogenesis. The relationship between fibrinogen-albumin ratio (FAR), serving as a novel inflammatory biomarker, and PMN is still unclear. Therefore, this study aims to clarify the association between FAR and disease activity and therapy response of PMN. Methods 110 biopsy-proven phospholipase A2 receptor (PLA2R) -associated PMN participants with nephrotic syndrome from January 2017 to December 2021 were recruited in the First Affiliated Hospital of Nanjing Medical University. The independent risk factors of non-remission (NR) and the predictive ability of FAR were explored by Cox regression and receiver-operating characteristic (ROC) curve analysis. According to the optimal cutoff value, study patients were categorized into the low-FAR group (≤the cutoff value) and the high-FAR group (>the cutoff value). Spearman’s correlations were used to examine the associations between FAR and baseline clinicopathological characteristics. Kaplan-Meier method was used to assess the effects of FAR on remission. Results In the entire study cohort, 78 (70.9%) patients reached complete or partial remission (CR or PR). The optimal cutoff value of FAR for predicting the remission outcome (CR + PR) was 0.233. The Kaplan-Meier survival analysis demonstrated that the high-FAR group (>0.233) had a significantly lower probability to achieve CR or PR compared to the low-FAR group (≤0.233) (Log Rank test, p = 0.021). Higher levels of FAR were identified as an independent risk factor for NR, and the high-FAR group was associated with a 2.27 times higher likelihood of NR than the low-FAR group (HR 2.27, 95% CI 1.01, 5.13, p = 0.048). These relationships remained robust with further analysis among calcineurin inhibitors (CNIs)-receivers. In the multivariate Cox regression model, the incidence of NR was 4.00 times higher in the high-FAR group than in the low-FAR group (HR 4.00, 95% CI 1.41, 11.31, p = 0.009). Moreover, ROC analysis revealed the predictive value of FAR for CR or PR with a 0.738 area under curve (AUC), and the AUC of anti-PLA2R Ab was 0.675. When combining FAR and anti-PLA2R Ab, the AUC was boosted to 0.766. Conclusions FAR was significantly correlated with proteinuria and anti-PLA2R Ab in PMN. As an independent risk factor for NR, FAR might serve as a potential inflammation-based prognostic tool for identifying cases with poor treatment response, and the best predictive cutoff value for outcomes was 0.233.

Orthognathic surgery improves compromised natural head position and pharyngeal airway in patients with Skeletal Class II or III malocclusion.

Natural head position (NHP), pharyngeal airway and maxillofacial growth pattern are correlated. The author's previous studies proved that following surgical correction of Skeletal Class II malocclusion, the over-extended NHP returned upright, and the pharyngeal airway space (PAS) dimension expanded. The present study compares the post-operative change in NHP and PAS after orthognathic surgery in Skeletal Class II and III malocclusion patients. Patients receiving orthognathic procedures to correct Skeletal Class II or III malocclusions were reviewed in this retrospective study. Pre-operative and 6-week post-operative cone-beam computed tomography datasets were collected. Variables representing the craniofacial pattern, the NHP and the PAS were measured three-dimensionally. Post-operative variables were compared with their pre-operative counterparts using either repeat-measure 2-way analysis of variance or Wilcoxon matched-pairs signed rank test. Thirty cases of Skeletal Class II malocclusion and 13 cases of Skeletal Class III malocclusion were collected. Preoperatively, the inter-group differences were significant in craniofacial pattern (68.14 ± 3.552 degree vs. 79.63 ± 2.497 degree, p < .0001) and the NHP (68.77 ± 11.02 degree vs. 82.83 ± 7.738 degree, p = .0002) while not significant in PAS; after surgery, the intergroup differences in craniofacial pattern and the NHP between groups decreased, and the PAS increased in both groups. Orthognathic surgery may improve compromised NHP and increase PAS in Skeletal Class II and III malocclusion patients.

A case series of fluoroscopy-guided neurolytic splanchnic nerve block for chronic pancreatitis pain

Context: Splanchnic nerve block (SPN) with local anesthetic and steroid is used to relieve the pain of chronic pancreatitis. However, it does not provide long-lasting relief. We hypothesize that the use of 70% alcohol will give adequate analgesia for more than months. Aims: The primary objective was to find out the analgesic efficacy of the use of 70% alcohol with SPN. Secondary objectives included the incidence of side effects, analgesic consumption postintervention, quality of life (QOL) assessed via a self-reported quality of life scale, and repeat block during the 1-year follow-up period. Settings and Design: Retrospective analysis of all patients with chronic pancreatitis who received bilateral SPN over the last 4 years. Methods and Materials: SPN was performed using the posterior retrocrural approach with the patient in the prone position as described in the literature using a 23 G × 90 mm spinal needle bilaterally at the level of T12 using C-arm/fluoroscopy guidance. Data were collected from the procedure book of the pain clinic and medical records. Statistical Analysis Used: Quantitative data for change in pre- to post-block VAS score was collected using the non-parametric Wilcoxon signed ranks test. Results: The baseline VAS, post-procedure VAS, and VAS at 3 months follow-up was 7.69 ± 1.3,2.44 ± 0.96 and 1.56 ± 1.15. A pairwise comparison of VAS performed between baseline and immediate post-procedure, baseline, and VAS at 3 months was found to be highly significant. Conclusions: Fluoroscopy-guided neurolytic SPN with 70% alcohol gives significant pain relief for more than 3 months. It also leads to improvement in 3 months QOL.

Quantifying Sagittal Lip Changes in Patients with Bilateral Cleft Lip Post Abbe Flap Reconstruction.

To objectively quantify results of sagittal lip changes following Abbe flap reconstruction in patients with bilateral cleft lip. Retrospective, observational study. Single institution, 8-year retrospective review. In total, 17 patients with bilateral cleft lip that underwent Abbe flap reconstruction were included in this study. Patients had lateral photographs taken prior to Abbe flap reconstruction and at least 8 months post-Abbe flap. Vegter's index, Sushner's S2 line and Burstone's B line reference lines were used for evaluation of sagittal lip changes. Wilcoxon signed rank tests were used in analysis. The mean pre-Abbe flap upper to lower lip ratio, defined as Vegter's Lip Index, was 0.906 compared to a mean of 0.946 following Abbe flap reconstruction. The mean upper to lower lip ratio for Sushner's S2 and Burstone's B line exhibited an increase in upper lip sagittal projection from -0.164 to 1.459 and 0.259 to 0.957, respectively (P < 0.001). This study quantifies sagittal changes to upper and lower lip position after Abbe flap reconstruction. These findings may aid in operative planning and patient/caregiver expectations during counseling.

Orofacial esthetics, chewing function, and oral health-related quality of life in Kennedy class I patients with mini-implant-retained removable partial dentures: A 3-year clinical prospective study.

92 participants with posterior edentulism in the maxilla or mandible received 184 MDIs and 92 RPDs. After one year, three participants were excluded, and another seven were excluded after three years. The final sample was 82 participants. Self-perceived orofacial esthetics was assessed by the Orofacial Esthetic Scale (OES), chewing function by the Chewing Function Questionnaire (CFQ), and the OHRQoL by the OHIP-14. Statistical analysis utilized multivariate regression analysis, standardized effect size calculation, Wilcoxon Signed Rank test, and Friedman's test. OHRQoL and chewing function significantly improved (p < 0.001) one month after MDI loading by the new RPDs and continued to improve over the observation period (p < 0.05). The OES also significantly improved (p < 0.001) and remained almost unchanged over the next three years (p = 0.440). Despite the limitations of this study, the MDI-retained RPD appears to be a viable treatment modality in contemporary prosthodontics from the patients' perspective.

Small cell osteosarcoma: An NCDB analysis of demographic and socioeconomic factors of diagnosed patients.

e23504 Background: Small cell osteosarcoma (SCOS) is a rare subtype of osteosarcoma accounting for roughly 1.5% of all osteosarcomas. Its prognosis is slightly worse than conventional osteosarcoma. Exploring demographic trends in patients with a confirmed SCOS diagnosis may provide insight into its epidemiology and allow for earlier diagnosis. The National Cancer Database (NCDB) was analyzed to research the demographic factors in patients diagnosed with SCOS. Methods: A retrospective cohort analysis utilizing the 2004–2020 National Cancer Database (NCDB) included patients with a histologically-confirmed diagnosis of SCOS (ICD-O-3 9185). Demographic factors (age, sex, race, Hispanic status, educational attainment, insurance status, facility type, distance from facility, and Charles-Deyo score) were analyzed via descriptive statistics. Incidence trends were interpreted in regression analysis. The mean survival was compared using the Log Rank (Mantel-Cox) test. Results: A cohort of 102 cases of SCOS were retrieved from the NCDB between 2004–2020. The primary sites for SCOS were the long bones of the lower limb (41%). Most patients were male (69%), White (63%), non-Hispanic (84%) with a mean age for diagnosis of 28 (SD = 18). The mean survival for males was 117 months (95% CI [93,141]), more than twice as long as females with 58 months (95% CI [31,85]). The Log Rank (Mantel-Cox) test reported a chi-square (χ²) value of 6.434, indicating a statistically significant difference between survival curves of males and females (p = 0.01). Residence in a metropolitan area (86%) was more common than other rural or urban areas. The greatest proportion of patients lived in the Middle or South Atlantic region of the United States (68%). The majority of patients were insured (86%), with the most covered by private insurance (64%) or Medicaid (22%). The median household income for each patient was most commonly in the highest quartile of over $74,063 (29%). Patients were diagnosed with SCOS at a steady rate between 2004 to 2020 (R² = 0.0956). Using the AJCC Cancer Staging System, most patients were Stage II (40%) or Stage IV (21%) at diagnosis. As a primary treatment, 87% of patients received chemotherapy. Most patients (91%) had no comorbidities with a Charlson-Deyo score of 0. Conclusions: This is the first time that demographic and socioeconomic factors of SCOS patients have been analyzed from the NCDB, revealing that the mean survival time of patients after receiving a diagnosis was more than double for males than females. SCOS patients are also more likely to live in metropolitan areas, particularly within the Middle or South Atlantic United States. Consistent with earlier reports, SCOS is typically diagnosed in young adults in the long bones of lower limbs. To better understand the impact of demographic factors on the diagnosis, treatment, and overall survival of patients with SCOS, further research is recommended.

Cross-project software defect prediction through multiple learning

Cross-project defect prediction is a method that predicts defects in one software project by using the historical record of another software project. Due to distribution differences and the weak classifier used to build the prediction model, this method has poor prediction performance. Cross-project defect prediction may perform better if distribution differences are reduced, and an appropriate individual classifier is chosen. However, the prediction performance of individual classifiers may be affected in some way by their weaknesses. As a result, in order to boost the accuracy of cross-project defect prediction predictions, this study proposed a strategy that makes use of multiple classifiers and selects attributes that are similar to one another. The proposed method's efficacy was tested using the Relink and AEEEM datasets in an experiment. The findings of the experiments demonstrated that the proposed method produces superior outcomes. To further validate the method, we employed the Wilcoxon sum rank test at 95% significance level. The approach was found to perform significantly better than the baseline methods.

Efficacy of chemotherapy followed by chemoradiation versus initial chemoradiation as part of the total neoadjuvant therapy for patients with locally advanced rectal cancer: An NCDB analysis.

e15629 Background: Results from multiple trials lead to modern management for locally advanced rectal cancer, with total neoadjuvant therapy (TNT) followed by surgery. However, the best sequence of different treatment modalities is unclear. Methods: We used the National Cancer Database (NCDB) to identify patients with locally advanced rectal adenocarcinoma. We divided patients into different categories based on the timing of chemo and radiation therapy relative to surgery. We used chi-square and Wilcoxon rank test for unadjusted comparison. To compare treatment efficacy with initial chemotherapy to concurrent chemoradiation in downstaging (clinical to pathological stage), we used a linear mixed effect model (LME) with adjustments on age, sex, race, facility type, and year of diagnosis. Also, we evaluated the probability of having positive lymph nodes in the pathological specimen (N+) in the multivariable logistic regression model with adjustment on the clinical stage in addition to the previously mentioned variables. All analyses were done using R 4.6.2. Results: A total of 100509 patients were identified. Only 695 patients received six cycles of neoadjuvant chemotherapy before concurrent chemoradiation (TNT chemotherapy), and 8677 patients received upfront radiation therapy with neoadjuvant chemotherapy administered within 12 weeks of neoadjuvant radiation therapy (TNT radiation). Patients whose start date of chemotherapy or radiation after surgery were excluded. The median age of participants was 63 (IQR = 54-63), and 83% were white. Patients who had TNT chemotherapy were younger (56.4 VS 59.5, P-value &lt; 0.01), had clinically and pathologically advanced stage (IIIB, IIIC) compared to TNT radiation (64%VS 37% and 33%VS 29%, P-value &lt; 0.01). Patients who received TNT radiation had an upgrade in their pathological stage compared to their clinical stage by 0.67 points in the LME (P value &lt; 0.01). In multivariable logistic regression. TNT chemotherapy had a 17% lower risk of (N+) with an OR of 0.83 (0.95 CI 0.59-1.16). However, it was not statistically significant. The two groups had no difference in OS, with a median OS of 137 months (0.95 CI 110 -NR) and 143 (0.95 CI 137-151), respectively. Conclusions: Upfront chemotherapy before starting chemoradiation could be associated with more significant downstaging. Future trials to validate our finding is warranted. [Table: see text] [Table: see text]

SORBS1 expression as a biomarker for obesity and breast cancer prognosis: Insights from genomic analysis and survival outcomes.

e13050 Background: Obesity is a known risk factor for breast cancer development and poorer survival. Correlation between the expression of the adaptor protein SORBS1 (Sorbin and SH3 domain-containing protein 1) and body mass index (BMI). Methods: Bioinformatics analysis. Results: We analyzed published datasets and plotted SORBS1 expression against patient BMI. Our findings show a negative correlation between SORBS1 expression and BMI in both datasets (R = -0.42, p = 0.00087, and R = -0.45 p = 0.00083, respectively). We also observed a negative correlation between SORBS1 expression and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) (R = -0.43, p = 0.00016). Additionally, we examined BMI-associated variants of the SORBS1 gene in the Qatar Biobank cohort of 15k individuals. We identified a total of 26 variants that were associated with an elevated risk for BMI in this population at a nominal significance. The top risk variant associated with the BMI is a missense variant (rs35480352; beta=0.058, p-value = 3.3e-03) with a frequency of 9.1% for the risk allele in our population. These results suggest that SORBS1 expression decreases with obesity and diabetes. This is significant because obesity is a known risk factor for breast cancer development and poorer survival. We also examined the SORBS1 gene expression in breast adenocarcinoma using UCSC TOIL RNA-seq recompute and TCGA-BRCA genomic and methylation data. Out of the 963 patients analyzed, only 12 (1.2%) showed any SORBS1 gene alteration, such as mutation (0.7%), amplification (0.2%), or deep deletion (0.3%), indicating a low occurrence of genomic alterations. Furthermore, our findings revealed no significant difference in SORBS1 methylation levels between the tumor and matched normal samples, indicating that the SORBS1 gene is not hypermethylated in breast carcinoma. Interestingly, our comparison of SORBS1 expression values between tumor and normal samples indicated significant under-expression in BRCA (log2FC = -2.7, p = 1.07E-127). SORBS1 expression was found to vary across various clinical stages (p = 0.0082, Kruskal-Wallis rank test), exhibiting a decline in advanced cancer stages. Moreover, we detected a significant difference in SORBS1 expression among different molecular subtypes (p &lt; 2E-16, Kruskal-Wallis rank test), with a lower expression level in more aggressive subtypes like HER2. Patients were classified into two groups according to their SORBS1 expression levels, using the median expression as a threshold: high and low. Conclusions: Our findings showed that the SORBS1 low group had substantially lower overall survival (log-rank p = 0.0024) and progression-free survival rates (log-rank p = 0.028). Silencing of SORBS1 in MCF-7 and MDA-MB-231 cells increased cell proliferation, migration, and invasion, underscoring its importance in breast cancer prognosis and as a target for intervention.

Examining 1-year mortality risk among patients with malignant melanoma undergoing immune checkpoint inhibitor therapy with a history of cannabis use.

11046 Background: Cannabis use has become an increased topic of discussion in the United States due to rise in legalization, thereby increasing its accessibility for recreational and medicinal use in diseases like cancer. Immune Checkpoint Inhibitor (ICI) therapy has also recently been increasing in patient with metastatic cancers such as melanoma by targeting PD1 or PD-L1 receptors to manipulate the body’s immune response to induce cancer cell death. Cannabis is mediated in part by the CB1 and CB2 receptors in the endocannabinoid system that is present in the natural immune system. Due to the body’s immune response to cannabis, it is hypothesized this could interfere with the activity of ICI therapy. However, research examining this is sparse. Therefore, the goal was to assess mortality in malignant melanoma patients with a history of cannabis use who undergo ICI therapy. Methods: A retrospective cohort study was performed with TriNetX, a federated database of ~100 million patients across 84 healthcare organizations. Patients &gt;17 years from 2012-2023 were identified based on ICI-therapy initiation within 1 month of malignant melanoma diagnosis. Cohorts were then created by history of those with and without cannabis use disorder. 1:1 propensity score matching was conducted to control for confounding comorbidities and demographics. Unadjusted and adjusted hazard ratios (aHR) with 95% CI were calculated for 1-year mortality after therapy initiation. HR’s were estimated using the Cox proportional hazard model. Survival curves were compared using the log-rank test. Results: A total 14589 melanoma patients who underwent ICI therapy were identified, of which 2.3% had documented cannabis use disorder. Prior to matching, melanoma patients with cannabis history had a statistically significant higher 1-year mortality compared to those with no cannabis history (HR [95%CI] = 1.29 [1.04,1.6], log rank test: p=0.0197). After matching, two balanced cohorts of 344 patients remained and adjusting for confounders revealed that melanoma patients with cannabis history had no significant difference in 1-year mortality risk compared to patients without cannabis history (1.18 [0.87,1.6], log rank test: p=0.293). Conclusions: Cannabis use among melanoma patients was shown to not have any meaningful difference in 1-year mortality risk compared to patients without cannabis use history while undergoing ICI-therapy. Additional studies, such as examining cannabis frequency and dosage, is warranted to further examine its effect.

Evaluation of biomarkers of response in patients with breast cancer with BRCA 1/2 pathogenic variants treated with PARP inhibitors.

e15188 Background: Several prospective studies highlight the pivotal role of PARP inhibitors (PARPi) in treating BRCA-associated breast cancers (BC), demonstrating a significant overall response rate (ORR) of up to 60% in advanced BC patients with BRCA 1/2 germline pathogenic variants (PV). Despite their clinical efficacy, the factors predicting PARPi response, the mechanisms of resistance to PARPi, and the clinical strategies to overcome these challenges are still unknown. The aim of this study is to establish tissue microarrays (TMA) from primary breast tumor tissue from BC patients with BRCA1/2 PVs who were treated with PARPi and identify biomarkers of PARPi resistance. Methods: Stage 4 BC patients with BRCA 1/2 PVs who presented to the University of Texas MD Anderson Cancer Center Breast Medical Oncology clinics and were treated with PARPi between 2008-2023 were identified using our database. Available patient tissue samples were obtained from institutional tumor banks. TMA from breast tumor tissue created and evaluated by our collabrating pathologists for expression of biomarkers:Wee-1, MRE, BP1,and c-Myc. Clinical and tumor characteristics analyzed included:Age at diagnosis, treatment details, tumor characteristics including histological type, hormonal receptor status, Her-2/Neu status, grade, Ki-67 and clinical outcome. Descriptive statistics, the Fisher exact test, and the log rank test were used to report patient characteristics and outcomes. Here we report on initial TMA construct and biomarker analysis. Results: So far TMA from 12 patients treated with PARPi were succesfully constructed. Patient characteristics include: Median age of 36.5 years (29-57). Nine (75%) and 3 (25%) patients had BRCA1 and BRCA2 mutations, respectively. All patients had invasive ductal carcinoma and 9 (75%) had triple negative BC. Most patient (75%) had high nuclear grade BC and median Ki-67 was 75 (15-90). In 11 evaluable patients, the ORR was 72.7%. The median OS was 383.6 months (95% CI 62.5-383.6) and median PFS was 31.5 months (95% CI 10.8-NE). No significant difference in biomarker expression was observed between PARPi-responders and non-responders (Table1). Conclusions: This report presents unique data on novel predictive biomarkers of response and evaluates the evidence for potential biomarkers. Further analysis on a larger TMA cohort is ongoing. [Table: see text]

The Impact of HAPPY (Humanity Assurance Protocol in Interventional Radiotherapy) on the Psychological Well-being of Gynecological Cancer Patients.

HAPPY (Humanity Assurance Protocol in interventional radiotherapy) reports the necessity for gynecological cancer patients to undergo interventional radiotherapy (IRT, also called brachytherapy). The present paper has evaluated how some precautions may improve the psychological well-being of the patients during IRT. Patients with gynecological cancer undergoing IRT-HDR were analyzed. Patients answered three questionnaires before the IRT procedure (T0) and at the end of IRT (T1): Distress Thermometer (DT), Numerical Rating Scale for IRT procedure distress (NRS), and Hospital Anxiety and Depression Scale (HADS). Correlations have been calculated pairwise through pandas. corrwith with a Pearson algorithm, and the p-values have been calculated through scipy.stats.pearsonr. Plots have been generated through seaborn and matplotlib. A Wilcoxon test was used. 55 patients were selected for this study. The median age of the patients was 64 (range, 39-84) years. 52 patients were with stage I endometrial cancer, whereas 3/3 patients with cervical cancer had locally advanced stages (IIB-IVA). 26 patients had a high education level (47.3%), and 38 were married or with a partner (69.1%). Only 14/55 (25.45%) patients were working. The HADS, DT, and NRS averages before the IRT procedure (T0) were 10.2, 3.8, and 4.3, respectively. After applying the HAPPY protocol, the HADS, DT, and NRS averages after IRT (T1) were 9.4, 3.4, and 2.6, respectively. The Wilcoxon signed rank test analysis showed a significant improvement in NRS (p < 0.00001) and HADS (p = 0.034). Living with a partner, parents or relatives was the only parameter statistically significantly associated with better DT pre-IRT (p = 0.04), HADS pre-IRT (p = 0.01), DT post-IRT (p = 0.01), and HADS post-IRT (p = 0.04). In our study, the HAPPY protocol was associated with a significant reduction in patients' distress, anxiety, and discomfort.

NaturalSpeech: End-to-End Text-to-Speech Synthesis With Human-Level Quality.

Text-to-speech (TTS) has made rapid progress in both academia and industry in recent years. Some questions naturally arise that whether a TTS system can achieve human-level quality, how to define/judge that quality, and how to achieve it. In this paper, we answer these questions by first defining the human-level quality based on the statistical significance of subjective measure and introducing appropriate guidelines to judge it, and then developing a TTS system called NaturalSpeech that achieves human-level quality on benchmark datasets. Specifically, we leverage a variational auto-encoder (VAE) for end-to-end text-to-waveform generation, with several key modules to enhance the capacity of the prior from text and reduce the complexity of the posterior from speech, including phoneme pre-training, differentiable duration modeling, bidirectional prior/posterior modeling, and a memory mechanism in VAE. Experimental evaluations on the popular LJSpeech dataset show that our proposed NaturalSpeech achieves -0.01 CMOS (comparative mean opinion score) to human recordings at the sentence level, with Wilcoxon signed rank test at p-level p >> 0.05, which demonstrates no statistically significant difference from human recordings for the first time.

Biologic and prognostic significance of HER2-low and ER-low expressions in de novo metastatic breast cancer.

e13170 Background: It is unclear whether ER-low-positive (ER-low) and HER2-low-positive (HER2-low) biomarkers, as new biological subtypes, have different biological and clinicopathological characteristics in de novo metastatic breast cancer (dnMBC). Per ASCO/CAP guidelines, tumors were defined as HER2-low-positive (HER2-low) if they had an HER2 immunohistochemical (IHC) score of 1+ or 2+ with negative in situ hybridization assay and HER2-0 if they had an HER2 IHC score of 0; ER-low refers to the tumor IHC staining of 1%-10%, if the staining is less than 1%, it is defined as ER-0. This study aimed to investigate whether ER-low and HER2-low expressions is associated with clinicopathologic characteristics and prognosis among patients with de novo metastatic breast cancer. The study was approved by the Ethics Committee of Hebei Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine (2017-AF29-058). Methods: Using hospital-based database, we identified patients with dnMBC diagnosed between 2010 and 2017, retrospectively collecting demographic data, tumor characteristics, treatment types, histopathological report and survival data. According to ASCO/CAP guideline recommendations, patient-specific histopathological results were classified, and IHC-based breast cancer markers, mainly including ER-low and HER2-low, were evaluated and analyzed. Median survival time (MST) was estimated by Kaplan-Meier method and log rank test. Univariable and multivariable analyses were performed using the Cox proportional hazard model to identify statistically significant prognostic factors. All statistical analyses were performed using Stata 18.0. Results: A total of 518 patients (median age of 53 years) were included in this study, including 194 patients with HER2-low, 201 patients with HER2-low, 36 patients with ER-low, and 179 patients with ER-0. Expression of HER2-low was significantly more common among ER-positive tumors (excluding the ER-low) compared with HER2-0 tumors (71.1% vs. 62.2%; P &lt; .001). The MST in the HER2-low cohort was longer than that in the HER2-0 cohort (40 vs. 30 months; HR,0.65; 95% CI, 0.52-0.82, p=.0001); while the MST of ER-low cohort was slightly longer than that of the ER-0 cohort (27 vs. 20 months; HR,0.75; 95% CI, 0.51-1.11, p=.231), but there was no statistical difference. Notably, in the metastasis pattern cohort, HER2-low showed a significantly higher MST compared with HER2-0 (P&lt;.001), with a MST of up to 68 months for bone-only metastases. There was no significant difference in MST between ER-low and ER-0 regardless of whether patients received endocrine therapy (P=.135). Conclusions: In the present study, for dnMBC patients, ER-low expression has similar biological and clinical outcome characteristics as ER-0. However, unlike HER2-0, HER2-low expression may predict a survival benefit in bone-only metastases.

Effect of timing of recurrence on outcomes in patients with metastatic breast cancer treated with CDK4/6 inhibitors.

e13067 Background: CDK4/6 inhibitors (CDKi) + endocrine therapy (ET) comprise the standard 1st line treatment for ER+ HER2- metastatic breast cancer (MBC). However, there is a gap in understanding how timing of MBC recurrence affects clinical outcomes on CDKi. We conducted a study to compare clinical outcomes of MBC patients on CDKi based on timing of MBC recurrence. Methods: This retrospective study enrolled ER+ HER2- MBC patients diagnosed from Jan 2015 to Jan 2023, who received CDKi + ET as 1st line treatment for MBC. Patients were categorized as de novo MBC (dMBC), if they had 1. Stage 4 disease at initial diagnosis or 2. MBC diagnosed &lt; 6 months of the primary breast cancer (PBC) diagnosis and before starting any systemic treatment for PBC. Patients with distant recurrence occurring &lt; 5 years, 5-10 years, and &gt;10 years from PBC were categorized as early, intermediate, and late MBCs (eMBC, iMBC, laMBC). Endpoints were Progression-Free Survival (PFS) and Overall Survival (OS) from MBC diagnosis. Baseline variables were compared using t-tests (continuous) and Chi-square tests (categorical). Endpoint analyses were conducted using Kaplan-Meier method and compared using Log rank test. Multivariate analyses were performed using Cox models. Results: Out of 280 patients enrolled, 67 were dMBC, 75 eMBC, 56 iMBC, and 82 laMBC. The laMBC group had a higher mean age (years) compared to other groups (71 vs. 62 in dMBC+ eMBC + iMBC, p&lt;0.001). 64.5% of laMBC had visceral disease compared to 50.5% of dMBC + eMBC + iMBC (p=0.031). 65.7% of dMBC patients were treated with palbociclib compared to 80.8% of eMBC + iMBC + laMBC (p=0.010). Higher % of eMBC were PR- vs other cohorts (41.3 vs 23.9 dMBC + iMBC + laMBC, p&lt;0.001). Among the 3 non dMBC groups, prior ET sensitivity (no recurrence for 2 years on adjuvant ET) was lower in eMBC (45.3%) compared to iMBC + laMBC (81.9%, p&lt;0.001). 61.3% of eMBC patients were on adjuvant ET at recurrence compared to 17.4% of iMBC + laMBC (p&lt;0.001). Other variables were similar. Table shows unadjusted endpoint analyses. In multivariate analyses, the risk of PFS events were not significantly different among cohorts (age&lt;=65, ECOG performance status (PS) &gt;=2 and PR- were independently associated with shorter PFS); risk of death was higher in eMBC vs laMBC (HR 1.73, p=0.047). Conclusions: In this retrospective study of ER+ HER2- MBC patients treated with 1st line CDKi + ET, timing of MBC recurrence was not associated with PFS differences after adjusting for other variables. However, patients with MBC recurring &lt; 5 years of PBC had the higher likelihood of death compared to those recurring &gt;10 years of PBC. [Table: see text]

Effects of Laghoo Shankaprakshalana (yogic colon cleansing) on anthropometric measurements in obese individuals.

Obesity is considered as one of the major public health burden and it is predictor of cardiovascular risk factor. Yoga is a mind-body medicine helps to promote health. This study was aimed to explore whether Laghoo Shankaprashalana (LS) reduce the body weight in obese individuals. This was a single group pre-post study. A total of 40 subjects (9 Male, 31 Female) aged between 18 and 40 years were recruited. This study was conducted in government yoga and naturopathy medical college, Chennai. Subjects were practiced weekly once LS for eight weeks (eight sessions). Subjects were assessed pre and post on body weight, body mass index, waist circumference, hip circumference, waist hip ratio, pulse rate and blood pressure. Variables were analyzed using Paired sample t test except waist hip ratio, which were analyzed using Wilcoxon's signed ranks test. There was significant reduction in the body weight (p<0.001, 5.81 %), Body Mass Index (p<0.001, 5.88 %), Waist Circumference (p<0.001, 7.20 %), Hip Circumference (p<0.001, 5.04 %), and Waist Hip Circumference (p<0.001, 3.19 %) after LS. However, there was no statistical significance difference in pulse rate, blood pressure. Eight sessions of Laghoo Shankaprakshalana helps to reduces body weight, body mass index, waist circumference, hip circumference and waist hip ratio. Reduction in the waist circumference might helps to reduce the cardiovascular risk. LS may be one of the cost effective intervention that can be incorporated in the weight loss regimen.

Testicular germ cell tumor survival among children, adolescents, and young adults: A population-based retrospective cohort study.

10035 Background: While testicular germ cell tumor (TGCT) overall survival (OS) exceeds 90%, some patient groups, such as adolescents, have inferior event free survival (EFS) outcomes. There is a paucity of granular, population-derived data about outcomes in children, adolescents, and young adults (CAYA) with TGCT, limiting a deeper understanding of the factors that impact their survival. Methods: All male CAYA (ages 11-21 years) in Ontario, Canada diagnosed with TGCT between 1992-2021 were identified using provincial cancer registries. Detailed disease and treatment characteristics were chart abstracted for ~2/3 of the cohort and determined through health administrative databases for the remainder. We assessed 5-year OS and EFS (first of death, recurrence/progression, or subsequent malignant neoplasm [SMN]) using Kaplan-Meier analysis and the log rank test. Follow-up started at TGCT diagnosis, except for survival after SMN or recurrence, where follow-up started at event date. Results: 748 TGCT patients were identified; 521 were chart abstracted and thus had EFS data available. Median age at diagnosis was 19 years (interquartile range:18-21) and 83.6% had non-seminoma histology. OS and EFS ± standard error (SE) were (94.7 ± 0.8 %, n=748) and (76.4 ± 1.9%, n=521), respectively. Among patients with chart abstracted data, OS and EFS differed by cancer extent at diagnosis and were lowest among CAYA with non-lung organ metastases (Table). Patients who underwent retroperitoneal lymph node dissection (RPLND) for initial treatment (91/521) had higher survival than those who did not (OS 96.6 ± 1.9% vs 93.7 ± 1.2%, p=0.04; EFS 87.6 ± 3.5 % vs 74.1 ± 2.1 %, p=0.0008), particularly CAYA with lung-only organ metastases. OS post SMN (n=28) was 77.3 ± 8.2%, with lower OS after non-TGCT SMN (50.8 ± 14.4%, n=13) than second primary TGCT (100 ± 0%, n=15), p=0.002. OS after recurrence/progression (n=116) was superior in the 59 who did not receive chemotherapy at initial diagnosis (89.7 ± 4%) compared to the 57 who had initial chemotherapy (65.9 ± 6.4%; p=0.0001). Conclusions: CAYA with TGCT have low EFS, consistent with previous studies. The extent of metastasis is a significant predictor. Efforts are needed to improve the survival outcomes of young TGCT patients with organ metastasis at diagnosis, and those who recur or develop a non-TGCT SMN. [Table: see text]