Higher Stage Research Articles

Sinonasal Mucosal Melanoma Survival Outcomes, Recurrence Patterns, and Prognostic Factors: A Systematic Literature Review and Meta-analysis of Publications after 2000

Abstract Background Sinonasal mucosal melanoma (SNMM) comprises <1% of all head and neck cancers but has one of the highest 5-year mortalities. Methods A systematic review and analysis using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta- Analyses) guidelines was conducted on SNMM survival, recurrence, and prognostic factors. Results A total of 2,379 abstracts were reviewed resulting in 90 studies describing 3347 SNMM patients. Patients were 49.65% male and 66.5 years old. Surgery plus radiation therapy, followed by surgery only, then radiation only were the most common treatments. Chemotherapy and immunotherapy were used in 418 patients and 101 respectively. The 2-, 3-, and 5-year overall survivals are 55.97, 40.09, and 30.35%, respectively. The 5-year disease-free survival and disease-specific survival are 25.56 and 38.04%. The 5-year local, regional, and distant recurrence-free survivals are 42.35, 81.64, and 44.65%. Mean survival after diagnosis was 26.99 months. Local (n = 650), regional (n = 226), and distant (n = 723) failure presented after 19.36, 6.35, and 12.42 months. Sites of metastasis were lung, liver, bone, brain, skin, kidney, and adrenal glands. Distant metastases, disease in the paranasal sinuses, and higher stage were noted to have worse survival outcomes. Positive margins did not significantly impact overall survival in 11/12 studies. Conclusion Overall survival over 20 years has remained poor with 70% of patients deceased in 5 years. About half of patients will develop distant failure and will thereafter rapidly decline. These data indicate need for advances in treatment of SNMM and new efforts with targeted immunotherapy offer a promising avenue toward improving survival outcomes.

FBXO2 as a switch guides a special fate of tumor clones evolving into a highly malignant transcriptional subtype in oral squamous cell carcinoma.

Tumors comprise a heterogeneous collection of tumor cells with distinct genetic and phenotypic characteristics that differentially promote malignant progression. Therefore, it is essential to depict the heterogeneous landscape of clones for understanding the cancer biology and overcoming the resistance of cancer therapy. To determine the dynamic clonal feature of OSCC, we constructed the evolutionary trajectory of tumor cells based on single-cell RNA sequencing data. A special transcriptional states of clones with distinct highly malignant features was identified, and FBXO2 was determined as the key switch gene causing the transition of tumor cells into this special state. FBXO2 exhibited a significantly high expression in OSCC than normal samples, especially in those with high clinical stages. The knockdown or overexpression of FBXO2 in OSCC cells correspondingly inhibited or promoted the abilities of proliferation, G1-S phase transition, migration, invasion, EMT, and resisting apoptosis. Moreover, FBXO2 was indicated to be involved in an intricate network to regulate multiple processes, modifying the interactions between tumor cells and other cells and thus defining different functional subtypes of tumor cells to affect tumor progression. These results provide new insights into clonal fate and pave the way for more effective therapy of OSCC.

Multinucleated tumor cells and micropapillary morphology appear to be predictors of poor prognosis in renal cell carcinoma with papillary and oncocytic features.

Renal cell carcinoma with papillary and oncocytic features (RCC-PO) are poorly understood, partially due to conflicting results in multiple studies. The histological features that predict behavior of RCC-PO have not been elucidated. The aim is to review clinicopathologic features and to correlate clinical outcomes of patients with RCC-PO to further expand our knowledge on these heterogeneous tumors. An archival search was done for "RCC" and "papillary," and tumors with >50% papillary and oncocytic features were included. Clinicopathologic data including tumor size, grade, stage, molecular and immunohistochemical testing when performed, and follow-up data were collected. Using multivariate analyses, correlation between histological features, tumor stage and prognosis were analyzed. Sixty-one patients with RCC-PO were identified of which 49 (80%) were male with a median age of 65 (range: 36-93) years, and a mean tumor size of 5.2 (range: 1-21.5) cm. Micropapillary features were seen in 4, bizarre nuclei (at least 3 times larger or with irregular shape) in 6, multinucleated tumor cells (MTC) in 15, single or small clusters (SSC) (made of 2-3 tumor cells) located away from areas of necrosis in 16, and striking eosinophilic cytoplasmic inclusions in 3 tumors, respectively. Thirty-six (59%) tumors were high-grade (WHO/ISUP grade 3-4), and 23 (38%) had a high stage (≥pT3 or pN1). Tumors were positive for AMACR (15/16) and CK7 (13/17), with preserved FH (7/7) staining and were all negative for CD117 (0/7), ALK, TFE3, cathepsin K, Melan A, and HMB45 (0/4, each). Three tumors underwent chromosomal microarray (CMA) plus gene fusion assay, and FISH and germline testing for FLCN and MET gene alterations by PCR were done on 1 each. Ten (16%) patients had a local recurrence (LR) or metastasis after nephrectomy; 4 died of disease (2 had tumors with micropapillary features), with a median follow-up of 7 (range: 0.01-19) years. Tumors with micropapillary features showed significantly higher RCC-PO-related mortality (50% vs. 3.5%, p<0.001). In multivariable analysis, SSC correlated with a higher stage (HR: 11.95; p=0.005); micropapillary features (HR: 18.42; p=0.017) and MTC (HR: 180.22; p=0.036) with presence of metastasis/LR; and micropapillary features with a higher RCC-PO-related mortality (HR: 60.35; p=0.036). RCC-PO are cytogenetically heterogeneous with overlapping features of various renal neoplasms. Micropapillary features and MTC appear to be independent predictors of poor outcomes in these tumors.

Gender-specific factors of suicidal ideation among high school students in Yunnan province, China: A machine learning approach.

Suicidal ideation (SI) assumes a pivotal role in predicting suicidal behaviors. The incidence of SI among high (junior and senior) school students is significantly higher than that of other age groups. The aim of this study is to explore the gender differences in SI among high school students in Yunnan Province. A total of 6180 students in grades 7-12 in Yunnan province, China from May 2021 to May 2022 participated in this survey. Univariate analysis was employed to describe the influencing factors of male and female students' SI. Subsequently, data were stratified by gender. Adopting machine learning technique, including Least Absolute Shrinkage and Selection Operator (Lasso) and Boruta algorithm, and logistic regression model to estimate the direction and effect magnitude of the influencing factors. The prevalence of SI was significantly higher for females (31.34%) than males (16.73%). The logistic regression model was established using the variables screened by Boruta algorithm, indicated that anxiety, depression, suffering emotion abuse or emotion neglect in childhood, non-suicidal self-injury, evening chronotype are common risk factors for SI in male and female students. Notably, female students who exhibited aggressive behavior, have experienced bullying, and were in the junior high school learning stage were more likely to report SI than their male counterparts. Females showed more vulnerability to SI than males especially among females in junior high school, reporting aggressive behavior and bullying experiences. Tailored prevention strategies, informed by these gender-related distinctions, should be developed and implemented.

Determinants of the serum potassium concentration in chronic kidney disease.

If Ccr is creatinine clearance, a surrogate for glomerular filtration rate (GFR), the serum potassium concentration (Ks) is the sum of EK/Ccr and TRK/Ccr, which are amounts of potassium excreted and (net) reabsorbed per volume of filtrate (Ks = EK/Ccr + TRK/Ccr). We investigated changes in EK/Ccr, TRK/Ccr, and Ks through the stages of chronic kidney disease (CKD). We performed a retrospective study of 452 patients with CKD stages G1 - 5. Simultaneous measurements of serum and urine potassium and creatinine concentrations (Ks, Ku, crs, and cru) were used to calculate 1,007 individual values of EK/Ccr and TRK/Ccr as Ku×crs/cru and Ks - EK/Ccr, respectively. Mean values of EK/Ccr and TRK/Ccr were determined in CKD stages G1 - 5. Within each stage, means of the ratios were also ascertained in subsets with hyperkalemia (Ks > 5.1 mmol/L), normokalemia (Ks 3.8 - 5.1 mmol/L), and hypokalemia (Ks < 3.8 mmol/L). In comparison to values in CKD stages G1 - 2, EK/Ccr rose and TRK/Ccr fell in each higher stage. Decrements in TRK/Ccr equaled increments in EK/Ccr in G3a and G3b, and Ks remained stable. In G4 - 5, the ascent of EK/Ccr exceeded the decline in TRK/Ccr, and Ks rose accordingly. Within each CKD stage, EK/Ccr was remarkably similar in the three kalemic subsets; consequently, differences in TRK/Ccr were the sole source of differences in Ks. EK/Ccr rises and TRK/Ccr falls through the stages of CKD. Ks remains stable in stages G3a - 3b in association with equal and opposite changes in EK/Ccr and TRK/Ccr. In stages G4 - 5, Ks increases progressively because EK/Ccr rises more than TRK/Ccr falls. Within each CKD stage, differences in TRK/Ccr account entirely for differences in Ks among hyper-, normo-, and hypokalemic subsets. Causes of variability of TRK/Ccr require additional investigation.

ZC3H13-induced the m6A modification of hsa_circ_0081723 promotes cervical cancer progression via AMPK/p53 pathway.

N6-methyladenosine (m6A) modification and circular RNAs (circRNAs) have been confirmed to participate in cervical cancer (CC) progression. However, the function of a novel circRNA, hsa_circ_0081723, has not yet been explored in CC. Therefore, this study aimed to investigate the potential role of hsa_circ_0081723 and its m6A modification in CC. The hsa_circ_0081723 and ZC3H13 expressions were examined by qRT-PCR in the CC tissues, and their prognostic significance was evaluated via Kaplan-Meier Plotter. The role of hsa_circ_0081723 in CC progression was checked by loss-of-function assays. The relative protein levels of AMPK/p53 pathway were determined by western blotting. The interactions of hsa_circ_0081723 and ZC3H13 were verified via MeRIP and RNA stability assays. The hsa_circ_0081723 expression was elevated in CC samples, and its higher levels indicated high histological grade, high FIGO stage, poor differentiation, and poor prognosis. Functionally, silencing hsa_circ_0081723 impaired the malignant behavior of CC cells and enhanced the protein levels of key molecules of the AMPK signaling pathway. Moreover, ZC3H13 was also elevated in CC samples and demonstrated a positive association with hsa_circ_0081723. The relative enrichment of hsa_circ_0081723 m6A and its stability were enhanced in ZC3H13 overexpressed CC cells. Mechanically, ZC3H13 overexpression partially reversed the antitumor effects caused by hsa_circ_0081723 knockdown in CC cells. This study innovatively demonstrates that ZC3H13-mediated m6A modification of hsa_circ_0081723 promotes CC progression by modulating AMPK/p53 pathway. Our findings may contribute to the understanding of the molecular mechanisms underlying CC and offer potential therapeutic targets for clinical treatment.

A New Algorithm Model Based on Extended Kalman Filter for Predicting Inter-Well Connectivity

Given that more and more oil reservoirs are reaching the high water cut stage during water flooding, the construction of an advanced algorithmic model for identifying inter-well connectivity is crucial to improve oil recovery and extend the oilfield service life cycle. This study proposes a state variable-based dynamic capacitance (SV-DC) model that integrates artificial intelligence techniques with dynamic data and geological features to more accurately identify inter-well connectivity and its evolution. A comprehensive sensitivity analysis was performed on single-well pairs and multi-well groups regarding the permeability amplitude, the width of the high permeable channel, change, and lasting period of injection pressure. In addition, the production performance of multi-well groups, especially the development of ineffective circulation channels and their effects on reservoir development, are studied in-depth. The results show that higher permeability, wider permeable channels, and longer injection pressure maintenance can significantly enhance inter-well connectivity coefficients and reduce time-lag coefficients. Inter-well connectivity in multi-well systems is significantly affected by well-group configuration and inter-well interference effects. Based on the simulation results, the evaluation index of ineffective circulation channels is proposed and applied to dozens of well groups. These identified ineffective circulation channel changing patterns provide an important basis for optimizing oil fields’ injection and production strategies through data-driven insights and contribute to improving oil recovery. The integration of artificial intelligence enhances the ability to analyze complex datasets, allowing for more precise adjustments in field operations. This paper’s research ideas and findings can be confidently extended to other engineering scenarios, such as geothermal development and carbon dioxide storage, where AI-based models can further refine and optimize resource management and operational strategies.

A Novel Quantitative Water Channeling Identification Method of Offshore Oil Reservoirs

Offshore oilfields are characterized by loose sandstone reservoirs, strong heterogeneity and high injection and production intensity. Water channeling gradually develops after entering the high water cut stage, which weakens production performance. Current identification methods usually have high computational costs and low efficiency. A quantitative identification model of water channeling based on inter-well connection units has been established by simplifying the complex reservoir system into a connection network between injectors and producers, which can quickly and accurately obtain strength characteristic parameters for waterflow channels. In addition, a comprehensive evaluation factor M and classification standard for water channeling suitable for offshore heterogeneous reservoirs have been proposed. It indicates a thief zone when M is larger than 0.65, a predominant waterflow channel when M is between 0.55 and 0.65, and no water channeling when M is smaller than 0.55. The application of (an) offshore S oilfield demonstrates that the new method successfully identifies 18 segments of the thief zone and 19 segments of the predominant waterflow channel and improves computational speed by 100 times compared with the conventional numerical modeling method. This novel method allows for rapid and accurate identification and prediction of water channeling, including location, directions, and strengths, thereby providing timely and practical guidance for inefficient water channel treatment.

Upper tract urothelial carcinoma: epidemiology, presentation, and high-risk endemic populations.

Upper tract urothelial carcinoma (UTUC) only accounts for 5-10% of all urothelial cancers but these patients present with high stage disease and 2 out of 3 patients have evidence of muscle-invasion at time of diagnosis. Furthermore, 10% of UTUC patients have associated Lynch syndrome and therefore diagnosis of UTUC should prompt timely evaluation and familial counseling. The purpose of this review is to outline the current evidence on the epidemiology, presentation, and high-risk endemic populations of UTUC through review of contemporary publications occurring over the preceding 18 months. Both the American Urological Association (AUA) and European Association of Urology (EAU) have published updated guidelines within the last 18 months for the management of UTUC. Of note, the updated guidelines give special consideration to identifying patients with risk factors for Lynch syndrome and recommend universal histologic testing for those with high probability of having Lynch syndrome cancers as well as referral for genetic counseling and germline testing. UTUC is an overall rare malignancy but tends to present with advanced stage and muscle-invasion. A proper understanding of the epidemiology, presentation, and high-risk endemic populations is necessary to develop preventive and interventional strategies.

Clinical relevance of protein-truncating variants of germline DNA repair genes in prostate cancer

BackgroundInterpreting genetic variants remains a challenge in prostate cancer (PCa). Although many annotation tools are available for prioritizing causal variants, the clinical relevance of these variants is rarely studied.MethodsWe collected a cohort study that included 274 PCa patients from June 2017 to December 2020 and sequenced 19 DNA damage repair (DDR) genes in these patients and explored the clinical consequence of these different approaches. We also examined all-cause and PCa-specific survival in DDR gene mutation carriers compared to non-carriers after androgen receptor (AR)-directed therapy.ResultsWe identified 13 variants from 19 DDR genes in a total of 14 (5.1%) patients who had at least one presumed pathogenic mutation using different annotation methods. Four variants were annotated as pathogenic, 11 variants were predicted as protein-truncating variants (PTVs), four variants received proxy-deleterious (Combined Annotation-Dependent Depletion scores of > 30), and only one variant was identified as a pathogenic variant or as having a functional effect by all three methods. PCa patients with PTVs were significantly associated with early onset, high cancer stage, and a worse response to AR-directed treatment. However, patients carrying a proxy-deleterious variant were only associated with a higher T (tumor) stage and N (node) stage than those without such a variant, but not associated with other clinical characteristics. In patients treated with AR-directed therapy, patients with a PTV showed an increased risk of all-cause death (adjusted hazard ratio (aHR) = 3.51, 95% confidence interval (CI): 1.06 ~ 11.56) and PCa-specific death (aHR = 4.49, 95% CI: 1.87 ~ 10.77) compared to non-PTV carriers after adjustment. We were unable to examine gene-specific risks due to the small number of patients.ConclusionsPTVs may assist in guiding treatment and early screening in PCa, while population-specific data for pathogenic variants are still being amassed.

The Influence of the Estrous Cycle on Neuropeptide S Receptor-Mediated Behaviors.

The Neuropeptide S receptor (NPSR) has been identified as a potential therapeutic target for anxiety and post-traumatic stress disorder. Central administration of Neuropeptide S (NPS) in male mice produces anxiolytic-like effects, hyperlocomotion, and memory enhancement. Currently, the literature is limited in the number of studies investigating the effects of NPS in female test subjects despite females facing a higher prevalence of anxiety-related pathology, as well as greater risk for adverse effects while taking psychoactive drugs. Moreover, no previous studies have considered the influence of estrous cycle on the effects of NPS. The current study investigates whether NPS-mediated behavioral phenotypes seen in males translate to females, and whether they are affected by estrous cycle stage. Female C57BL/6NCr mice were intracerebroventricularly (ICV) cannulated and underwent behavioral paradigms to test locomotion, anxiety, and memory. Estrous cycle stage was determined through examination of vaginal cytology. Our results provide evidence that NPS-mediated behaviors are influenced by the estrous cycle. Administration of NPS decreased anxiety-like behaviors more robustly when the female mice were in high estrogen stages of the estrous cycle. Therefore, the desired anxiolytic-like effects of targeting the NPSR are intact in female mice. However, these effects may to be influenced by the stage of the estrous cycle. The NPSR remains a strong potential drug target for new anxiolytic compounds and based on our initial observations further studies exploring the interaction of estrous cycle and the NPS-system are warranted. Significance Statement The neuropeptide S (NPS) receptor has been identified as a potential target for treating anxiety, a condition that is most prevalent in females. Therefore, the potential interaction of estrous cycle with the NPS-system described in the current study is an important first step in understanding the function of the NPS-system in females.

A multimodality score strategy for assessing the risk of immune checkpoint inhibitors related cardiotoxicity

This study aimed to find the association between four common clinical biomarkers and subsequent ICICT, developing a risk scoring strategy to assess the ICICT risk. Three terminals for ICICT were : Terminal 1, cancer therapy-related cardiomyopathies; Terminal 2, myocarditis or heart failure; and Terminal 3, myocarditis, heart failure, myocardial infarction, cerebral infarction, atrial fibrillation, or death. The thresholds were : N-terminal-pro-B-type-natriuretic-peptide ≥ 125 pg/mL, cardiac troponin T ≥ 6 ng/L, high-sensitivity C-reactive protein ≥ 3 mg/L, and coronary artery calcium score > 10 U. Each of the four abnormal biomarkers received 1 point. The links between biomarkers, score stage, and ICICT were analyzed. 375 patients with a mean follow-up of 1.91 years were included. All four biomarkers measured before immunotherapy were associated with a higher risk of developing ICICT. These scores were also associated with ICICT risk. The highest risk was the very high stage (score = 4) has 7.29, 8.83, and 7.02 folder higher risk compared to low risk group for Terminal 1–3, respectively. The cumulation of incidences also showed that the higher stages of score had an earlier onset and higher incidence of ICICT. 4 biomarkers and the scoring strategy enables clinicians to assess risk easily.

The clinical outcome, pathologic spectrum, and genomic landscape for 454 cases of salivary mucoepidermoid carcinoma

Mucoepidermoid carcinoma (MEC) is the most common malignant salivary tumor. A complete understanding of the high heterogeneity of MEC in histology and genetics would help in accurate diagnosis and treatment. Therefore, We evaluated the clinical features, treatment outcomes, and pathological parameters of 454 MECs and analyzed their genomic features using whole-exome sequencing and whole-transcriptome sequencing. We found that MECs predominantly occurred in females and those in their 4th–5th decades. The parotid gland was the most frequently affected site. All patients underwent complete mass resection with lobectomy; 414 patients were alive without relapse at follow-up, after an average period of 62 months (1–116 months). The disease progressed after initial treatment in 40 patients. The lungs were the most common site of distant metastasis. For classical MECs, histologic gradings of the AFIP, modified Healey, and MSK systems were significantly associated with recurrence and lymph nodal metastasis; these gradings were significantly related to lymph nodal metastasis for the subtypes. Older age, minor salivary gland involvement, clinical symptoms, high TNM stage, high-grade tumor, and improper surgical modality were the main prognostic factors. BAP1 was the most frequently mutated gene in MEC. Mutations in CDKN2A, MET, and TP53 were more frequently found in aggressive tumor phenotypes. MAML2 rearrangement was observed in 42% of patients, and EWSR1 rearrangement in 8%. Specific genetic events (in TP53 and FBXW7) with CRTC1::MAML2 fusion superimposed might be associated with unfavorable prognosis. This study provides new insights into precision therapeutic strategies for MEC.

Stability‐Enhanced Variable Stiffness Metamaterial with Controllable Force‐Transferring Path

AbstractSelf‐contact variable stiffness (SVS) metamaterial offers specific patterns of elastic strain energy storage by changing its force‐transferring path. The change of the elastic strain energy storage patterns further influences the stiffness variation of the SVS metamaterials. However, challenges still arise because typically fabricated SVS metamaterials inevitably contain structural irregularities, eccentricities, and defects. These microstructural imperfections impede the stable generation of designed strain energy storage patterns in the metamaterial, implying that the SVS metamaterials cannot achieve expected stiffness variations. To address this burning question, an SVS metamaterial/meta‐structure design paradigm with eccentric unit designs is proposed, which can realize both stable stiffness variations and high load‐bearing. The theoretical, simulation, and experimental results demonstrate that the SVS chain meta‐structure achieves ≈110 times stiffness variation between the low and high loading conditions. Its load‐bearing can reach more than 1500 N when the meta‐structure falls into the high stiffness stage. Furthermore, some typical functions are demonstrated using the stability‐enhanced SVS metamaterial, including customized mechanical protections for human joints and information transformation regulated by remote mechanical input signals. The results can provide a useful solution for generating a more feasible stability‐enhanced SVS metamaterial/meta‐structure and promote their potential applications in aerospace, medical devices, and robotics.

Investigation on heat recovery strategies from low temperature food processing plants: Energy analysis and system comparison

Industrial food processing plants often have significant thermal requirements at both low and high temperatures. These plants can produce a variety of products including frozen, chilled and grilled/steamed foodstuff, creating thermal demands at several temperature levels. Rapid freezing of the foodstuff at temperatures below -40 °C is required to preserve a high-quality product while steaming/grilling of foodstuff require heat above 100 °C. Heat recovery from the low-temperature refrigeration system provides an interesting opportunity to reduce the overall energy consumption of the plant. This paper presents different strategies to achieve heat recovery from a CO2/NH3 cascade refrigeration system. The low stage of the cascade features pumpcirculated CO2 circuits at -40 °C and -5 °C evaporation levels, while the high temperature stage consists of an ammonia circuit. For this investigation, a case is defined based on requirements for temperature level and heat quantity from the industry. Subsequently, different strategies for the integration and control of the energy systems are examined. Finally, the strategies are compared with selected key parameters and the results are presented. This article is a translation of the article by Ahrens MU, Selvnes H, Henke L, Bantle M, Hafner A. Investigation on heat recovery strategies from low temperature food processing plants: Energy analysis and system comparison. In: Proceedings of the 9th IIR Conference on the Ammonia and CO2 Refrigeration Technologies. Ohrid: IIF/IIR, 2021. DOI: 10.18462/iir.nh3-co2.2021.0034 Published with the permission of the copyright holder.

SERPINH1 as a Novel Biomarker for Colon Cancer Bone Metastasis with Machine Learning and Immunohistochemistry Validation.

Background: Bone metastasis (BM) is a serious clinical symptom of advanced colorectal cancer. However, there is a lack of effective biomarkers for early diagnosis and treatment. Method: RNA-seq data from public databases (GSE49355, GSE101607) were collected and normalized and batch effects were removed using the combat package. Differential expression analysis was performed to identify significant genes. Robust Rank Aggregation and machine learning algorithms were used to pinpoint candidate biomarkers. These biomarkers were validated using immunohistochemistry and further analyzed for survival rates. Enrichment analysis was conducted to explore biological mechanisms. Additionally, drug sensitivity and immune infiltration analyses were performed to provide insights into potential therapeutic targets. Results: Analysis results revealed 386 genes elevated in primary versus normal tissues and 26 genes varying between primary and BM. Serpin Protease Inhibitor Clade H1 (SERPINH1) as a novel biomarker for colon cancer metastasis. High SERPINH1 expression correlates with poor survival outcomes and is linked to high lymphatic invasion and advanced cancer stages. Additionally, SERPINH1 expression influences immune infiltration and is not predictive of chemotherapy response, but potential new drugs are suggested for high-expression cases. The gene also enriches classical cancer pathways such as Hedgehog and transforming growth factor-β. Conclusions: We identified novel colon cancer BM markers, including SERPINH1, using machine learning algorithms combined with traditional transcriptomic data and validated their expression through immunohistochemistry. This biomarker could significantly assist clinicians in making more precise treatment decisions.

Prognostic Value and Clinical Implication of Lymph Node-to-Primary Tumor SUV Ratio in Node-Positive Hypopharyngeal Squamous Cell Carcinoma Treated With Radiotherapy With or Without Chemotherapy.

The aim of this was to evaluate the prognostic significance of the nodal-to-primary tumor SUVmax ratio (NTR) in patients with node-positive hypopharyngeal squamous cell carcinoma (HPSCC) treated with radiotherapy with or without concurrent chemotherapy. The study aims to enhance prognostic accuracy by incorporating NTR into the American Joint Committee on Cancer (AJCC) staging system. This retrospective study included 191 patients with biopsy-proven node-positive HPSCC treated from 2005 to 2013. NTR was calculated as the ratio of SUVmax of metastatic lymph nodes to the primary tumor's SUVmax. Survival analyses were conducted using Cox regression models and Kaplan-Meier analysis. Receiver operating characteristic analysis compared the prognostic performance of the modified and AJCC staging systems. The median follow-up was 8.27 years, with 135 deaths (70.7%). High NTR (≥0.63) was significantly associated with worse overall survival (OS) and was an independent prognostic factor in multivariable analysis (adjusted hazards ratio [HR] = 1.63, P = 0.007). Median OS for high NTR was 17.4 months, compared with 75.2 months for low NTR. High NTR significantly predicted worse OS within AJCC stage IVA patients (HR = 6.09, P = 0.014). Patients in modified stage IVA (AJCC stage IVA with low NTR) had significantly longer OS than those in modified stage IVB (AJCC stage IVA with high NTR and AJCC stage IVB) (HR = 8.62, P = 0.003). The modified staging system incorporating NTR showed superior prognostic performance compared with the AJCC staging system. NTR is a significant independent prognostic factor for OS in node-positive HPSCC patients. Integrating NTR into the AJCC staging system improves prognostic accuracy.

Mechanisms and models of interface trap annealing in positively-biased MOS devices

Abstract We propose a hydrogen anion (H$^-$) passivation mechanism of the interface trap annealing (ITA) in positively-biased metal-oxide-semiconductor (MOS) devices. It is demonstrated that, the protons (H$^+$) released in SiO$_2$ due to H$_2$ cracking on oxide traps can migrate into Si at relatively high temperature, therefore passivating the interfacial $P_b$ centers by capturing two electrons provided by the positive bias. This new mechanism explains the elimination temperature of about 100$^\circ$C in experiments, which is much lower than temperature above 220$^\circ$C predicted by the traditional H$_2$ passivation mechanism. We also derive analytic models of the ITA, based on the coupling transformation dynamics of oxide and interface traps, as well as the concept of hierarchically constrained dynamics in glassy materials. These models can universally describe a generation-to-elimination transition of $P_b$, and predict the enhanced elimination of $E'_\gamma$ as the annealing temperature is elevated. Moreover, we demonstrate that, the defect annealing models can be applied to analysis the nonmonotonic temperature dependence of the annealing of threshold voltage shift in nMOS devices. Our findings provide a theoretical basis for achieving the low temperature elimination of interface traps, and for setting the high temperature stages of accelerated aging and damage evaluations of MOS devices.

Selective Extrauterine Placental Perfusion in Monochorionic Twins Is Feasible-A Case Series.

Monochorionic (MC) twins are at risk for severe twin-to-twin transfusion syndrome (TTTS) or twin anemia-polycythemia sequence (TAPS). In the case of preterm delivery, cesarean section (CS) with immediate umbilical cord clamping (ICC) of both twins is usually performed. While the recipient is at risk for polycythemia and may benefit from ICC, this procedure may result in aggravation of anemia with increased morbidity in the anemic donor. The purpose of this study was to demonstrate that the novel approach of selective extrauterine placental perfusion (EPP) with delayed umbilical cord clamping (DCC) in the donor infant is feasible in neonatal resuscitation of MC twins and may prevent severe anemia in donor and polycythemia in the recipient. Preterm MC twins with antenatal suspected severe anemia of the donor as measured by Doppler ultrasound, born with birthweights < 1500 g by CS, were transferred to the neonatal resuscitation unit with placenta and intact umbilical cords. In the donor, the umbilical cord was left intact to provide DCC with parallel respiratory support (EPP approach), while the cord of the recipient was clamped immediately after identification. Selective EPP was performed in three cases of MC twins with TAPS and acute peripartum TTTS. All donor twins had initial hemoglobin levels ≥ 13.0 g/dL, and none of them required red blood cell transfusion on the first day after birth. Selective EPP may be a feasible strategy for neonatal resuscitation of MC preterm twins with high stage TAPS and TTTS to prevent anemia-related morbidities and may improve infant outcome.

Phonocardiogram (PCG) Murmur Detection Based on the Mean Teacher Method.

Cardiovascular diseases (CVDs) are among the primary causes of mortality globally, highlighting the critical need for early detection to mitigate their impact. Phonocardiograms (PCGs), which record heart sounds, are essential for the non-invasive assessment of cardiac function, enabling the early identification of abnormalities such as murmurs. Particularly in underprivileged regions with high birth rates, the absence of early diagnosis poses a significant public health challenge. In pediatric populations, the analysis of PCG signals is invaluable for detecting abnormal sound waves indicative of congenital and acquired heart diseases, such as septal defects and defective cardiac valves. In the PhysioNet 2022 challenge, the murmur score is a weighted accuracy metric that reflects detection accuracy based on clinical significance. In our research, we proposed a mean teacher method tailored for murmur detection, making full use of the Phyionet2022 and Phyionet2016 PCG datasets, achieving the SOTA (State of Art) performance with a murmur score of 0.82 and an AUC score of 0.90, providing an accessible and high accuracy non-invasive early stage CVD assessment tool, especially for low and middle-income countries (LMICs).