Multiview learning with twin parametric margin SVM.

Multiview learning (MVL) seeks to leverage the benefits of diverse perspectives to complement each other, effectively extracting and utilizing the latent information within the dataset. Several twin support vector machine-based MVL (MvTSVM) models have been introduced and demonstrated outstanding performance in various learning tasks. However, MvTSVM-based models face significant challenges in the form of computational complexity due to four matrix inversions, the need to reformulate optimization problems in order to employ kernel-generated surfaces for handling non-linear cases, and the constraint of uniform noise assumption in the training data. Particularly in cases where the data possesses a heteroscedastic error structure, these challenges become even more pronounced. In view of the aforementioned challenges, we propose multiview twin parametric margin support vector machine (MvTPMSVM). MvTPMSVM constructs parametric margin hyperplanes corresponding to both classes, aiming to regulate and manage the impact of the heteroscedastic noise structure existing within the data. The proposed MvTPMSVM model avoids the explicit computation of matrix inversions in the dual formulation, leading to enhanced computational efficiency. We perform an extensive assessment of the MvTPMSVM model using benchmark datasets such as UCI, KEEL, synthetic, and Animals with Attributes (AwA). Our experimental results, coupled with rigorous statistical analyses, confirm the superior generalization capabilities of the proposed MvTPMSVM model compared to the baseline models. The source code of the proposed MvTPMSVM model is available at https://github.com/mtanveer1/MvTPMSVM.

The spatial distribution of intermediate fibroblasts and myeloid-derived cells dictate lymph node metastasis dynamics in oral cancer.

BACKGROUND: Oral cancer poses a significant health challenge due to limited treatment protocols and therapeutic targets. We aimed to investigate the invasive margins of gingivo-buccal oral squamous cell carcinoma (GB-OSCC) tumors in terms of the localization of genes and cell types within the margins at various distances that could lead to nodal metastasis. METHODS: We collected tumor tissues from 23 resected GB-OSCC samples for gene expression profiling using digital spatial transcriptomics. We monitored differential gene expression at varying distances between the tumor and its microenvironvent (TME), and performed a deconvulation study and immunohistochemistry to identify the cells and genes regulating the TME. RESULTS: We found that the tumor-stromal interface (a distance up to 200 µm between tumor and immune cells) is the most active region for disease progression in GB-OSCC. The most differentially expressed apex genes, such as FN1 and COL5A1, were located at the stromal ends of the margins, and together with enrichment of the extracellular matrix (ECM) and an immune-suppressed microenvironment, were associated with lymph node metastasis. Intermediate fibroblasts, myocytes, and neutrophils were enriched at the tumor ends, while cancer-associated fibroblasts (CAFs) were enriched at the stromal ends. The intermediate fibroblasts transformed into CAFs and relocated to the adjacent stromal ends where they participated in FN1-mediated ECM modulation. CONCLUSION: We have generated a functional organization of the tumor-stromal interface in GB-OSCC and identified spatially located genes that contribute to nodal metastasis and disease progression. Our dataset might now be mined to discover suitable molecular targets in oral cancer.

Assessment of nitrosamine exposure in Korean foods: analysis, risk evaluation, and implications.

This study investigated the presence of nitrosamines, known carcinogens, in 1320 food samples from South Korea using LC-APCI-MS/MS analysis. Results showed nitrosamines were detected in 72% of samples, with processed foods exhibiting higher levels. Sesame oil, snow white rice cake, fried chicken wings, and fried squid were identified as having the highest nitrosamine content. Daily intake estimates revealed nitrosodiethylamine (NDEA), nitrosodibutylamine (NDBA), and nitrosopyrrolidine (NPYR) as major contributors to exposure. Risk assessment, based on BMDL10 values and MOE calculations, indicated low health risks overall, but certain food groups at the 95th percentile showed MOEs below the safety threshold, warranting attention. This underscores the need for ongoing monitoring and regulation of nitrosamine levels in food products to protect public health, particularly in regions with high consumption of processed foods like South Korea. Further research and regulatory measures are crucial to minimize nitrosamine exposure and mitigate associated health risks. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-024-01651-8.

Composition of e-cigarette aerosols: A review and risk assessment of selected compounds.

The potential harms and benefits of e-cigarettes, or electronic nicotine delivery systems (ENDS), have received significant attention from public health and regulatory communities. Such products may provide a reduced risk means of nicotine delivery for combustible cigarette smokers while being inappropriately appealing to nicotine naive youth. Numerous authors have examined the chemical complexity of aerosols from various open- and closed-system ENDS. This body of literature is reviewed here, with the risks of ENDS aerosol exposure among users evaluated with a margin of exposure (MoE) approach for two non-carcinogens (methylglyoxal, butyraldehyde) and a cancer risk analysis for the carcinogen N-nitrosonornicotine (NNN). We identified 96 relevant papers, including 17, 13, and 5 reporting data for methylglyoxal, butyraldehyde, and NNN, respectively. Using low-end (minimum aerosol concentration, low ENDS use) and high-end (maximum aerosol concentration, high ENDS use) assumptions, estimated doses for methylglyoxal (1.78 × 10-3-135 µg/kg-bw/day) and butyraldehyde (1.9 × 10-4-66.54 µg/kg-bw/day) corresponded to MoEs of 227-17,200,000 and 271-280,000,000, respectively, using identified points of departure (PoDs). Doses of 9.90 × 10-6-1.99 × 10-4 µg/kg-bw/day NNN corresponded to 1.4-28 surplus cancers per 100,000 ENDS users, relative to a NNN-attributable surplus of 7440 per 100,000 cigarette smokers. It was concluded that methylglyoxal and butyraldehyde in ENDS aerosols, while not innocuous, did not present a significant risk of irritant effects among ENDS users. The carcinogenic risks of NNN in ENDS aerosols were reduced, but not eliminated, relative to concentrations reported in combustible cigarette smoke.

Suppressing a ß-1,3-glucanase gene expression increases the seed and fibre yield in cotton.

Seeds are initiated from the carpel margin meristem (CMM) and high seed yield is top one of breeding objectives for many crops. ß-1,3-glucanases play various roles in plant growth and developmental processes; however, whether it participates in CMM development and seed formation remains largely unknown. Here, we identified a ß-1,3-glucanase gene (GLU19) as a determinant of CMM callose deposition and seed yield in cotton. GLU19 was differentially expressed in carpel tissues between Gossypium barbadense (Gb) and Gossypium hirsutum (Gh). Based on resequencing data, one interspecies-specific InDel in the promoter of GLU19 was further detected. The InDel was involved in the binding site of the CRABS CLAW (CRC) transcription factor, a regulator of carpel development. We found that the CRC binding affinity to the GLU19 promoter of G. barbadense was higher than that of G. hirsutum. Since G. barbadense yields fewer seeds than G. hirsutum, we speculated that stronger CRC binding to the GLU19 promoter activated higher expression of GLU19 which in turn suppressed seed production. Consistent with this hypothesis was that the overexpression of GhGLU19 caused reduced seed number, boll weight and less callose formation in CMM. Conversely, GhGLU19-knockdown (GhGLU19-KD) cotton led to the opposite phenotypes. By crossing GhGLU19-KD lines with several G. hirsutum and G. barbadense cotton accessions, all F1 and F2 plants carrying GhGLU19-KD transgenic loci exhibited higher seed yield than control plants without the locus. The increased seed effect was also found in the down-regulation of Arabidopsis orthologs lines, indicating that this engineering strategy may improve the seed yield in other crops.

The mode of circumferential margin involvement in rectal cancer determines its impact on outcomes: A population-based study.

BACKGROUND: The clinical value of different modes of CRM involvement in rectal cancer patients is unclear. This study aims to determine the clinical impact of different modes of circumferential resection margin (CRM) involvement in patients with a locally advanced rectal carcinoma. PATIENTS AND METHODS: A cohort of patients who were diagnosed with stage III rectal cancer between June 2014 and June 2020 was selected from the prospective Dutch nationwide pathology databank (PALGA). Histopathological and clinical data were analyzed according to the nature of CRM involvement (via primary tumor invasion, lymph node metastasis, tumor deposit, multiple factors) and analyses on recurrence and overall survival (OS) were performed. RESULTS: 3020 patients were included, of whom 12.4 % had a positive CRM. The majority of these patients (63.2 %) had CRM involvement by primary tumor invasion and in 9 % of patients multiple factors caused the positive CRM. The rates of local recurrence and distant metastasis were related to the nature of the CRM involvement, with lowest rate for lymph node metastasis and highest rate for multiple factors. On multivariate analysis, CRM involvement by primary tumor invasion, tumor deposits and multiple factors, but not by lymph node metastasis, were associated with poor OS. CONCLUSION: This nationwide population based study highlights the clinical importance of reporting the nature of CRM involvement in rectal cancer patients. Lymph node metastasis involving the CRM does not bear the same risks for local recurrence, distant metastases and OS as CRM involvement by primary tumor invasion or CRM involvement by multiple factors.

Technologies and techniques to improve precision in breast conserving surgery.

Imprecision in breast conserving surgery results in high rates of take back to theatre for reexcision of margins. This paper reviews the various approaches to improving the precision of oncological margin control in breast conserving surgery. The review describes the rationale for improved tissue characterization over tumor localization and explores technology-free approaches, as well as progress being made to develop and test innovative technological solutions.

Margin status of basal cell carcinoma: What can be done better?

PURPOSE: Guidelines on clinical margins for basal cell carcinoma (BCC) excisions were recently published, yet the ambiguity regarding the margin continues for surgeons and pathologists. The purpose of this study was to determine the incomplete excision rate of BCC, determine the factors associated with incomplete excision, and evaluate the completeness of reporting between surgeon and pathologist. METHODS: A single-center retrospective analysis was conducted on pathology reports from single excisions of BCC specimens between January 1, 2019 to December 31, 2020. The primary outcome was the incomplete excision rate (positive margins) as reported by pathologist. Logistic regression was used to determine the relationship between incomplete excision rate and anatomical location, pathologist, and surgeon. The completeness of surgeon pathology requisition forms was evaluated qualitatively. RESULTS: Seven hundred and fifty-six pathology reports were included. The incomplete excision rate was 12% (n = 94). The most common site of incomplete excision was head and neck (n = 87, 15%), followed by trunk (n = 5, 7%), and extremities (n = 2, 2%). Five hundred and seventy-nine specimens from 6 surgeons and 9 pathologists were included in the logistic regression analysis. The Wald test showed that the location was significantly associated with incomplete excision (p < 0.05), whereas surgeon and pathologist reports were not (p > 0.05). Regarding missing information, only 47 (6%) pathology reports included "excision" in the requisition form. Four hundred and three (53%) specimens had no clinical history. CONCLUSIONS: The incomplete excision rate found in this study falls within the report range in the literature. Neither surgeon nor pathologist had significant association with incomplete excision. Incomplete excision rate of BCC may be inflated owing to the lack of standardization in requisition form and pathology reporting.

Modified Two-Step Impressions via the Incorporation of Venting Holes: A Technical Report.

This study presents a methodology for obtaining a precise impression of the crown margin of prepared teeth by utilizing a two-step impression technique. The method begins with the fabrication of a custom tray made from heat-cured acrylic resin, followed by the acquisition of an initial impression using putty elastomeric material. Subsequently, the impression is relieved around the prepared teeth, and vent holes are strategically placed through both the impression and the tray. Finally, a light-body consistency impression material is applied. This streamlined technique enhances efficiency and minimizes the errors commonly encountered with traditional two-step impression methods.

Vertical margin distance in T1 colorectal carcinoma resected by endoscopic submucosal dissection affects prognosis after additional surgery.

PURPOSE : A vertical margin (VM) distance of < 500 µm is a risk factor for recurrence in patients with T1 colorectal carcinoma (CRC) resected by endoscopy. We aimed to determine the effects of the VM distance on the recurrence and prognosis of T1 CRC. METHODS: We enrolled 168 patients with T1 CRC who underwent additional surgery after endoscopic submucosal dissection (ESD) at multiple centers between 2008 and 2016. None of the patients were followed up for < 5 years. The enrolled 168 patients were classified into patients with VM distance of < 500 µm including positive VM (n = 72 [43%], VM distance < 500 µm group) and patients with VM distance of ≥ 500 µm (n = 96 [57%], VM distance ≥ 500 µm group). The clinicopathological features, recurrence rates, and prognoses were compared between the groups using propensity-score matching (PSM). RESULTS: Tumors recurred in eight of the 168 patients (5%) with VM distance < 500 µm. After PSM, the rate of overall recurrence and local recurrence in the VM distance < 500 µm group were significantly higher than those in the VM distance ≥ 500 µm group. The 5-year recurrence-free survival rate was significantly higher in the VM distance ≥ 500 µm group than that in VM distance < 500 µm group after PSM (100% vs. 89%, p < 0.012). CONCLUSIONS: Complete en bloc resection of T1 CRC via ESD must include a sufficient amount of SM to reduce the risk of metastasis and recurrence after additional surgery.

Immediate and delayed flap reconstruction have equivalent outcomes and associated costs following soft tissue sarcoma surgery.

BACKGROUND AND OBJECTIVES: Surgical treatment of soft tissue sarcoma (STS) involves wide resection of the tumor, which can necessitate soft tissue reconstruction with local or free tissue flaps. This retrospective study compares cost, surgical and oncologic outcomes between patients undergoing reconstruction with immediate versus delayed flap coverage following STS resection. METHODS: Thirty-four patients who underwent planned flap reconstruction following resection of primary STS were identified retrospectively. Twenty-four (71%) received immediate reconstruction during the index surgery and 10 (29%) underwent planned delayed reconstruction. Preoperative patient-specific metrics, tumor characteristics, and surgical and patient outcomes were collected. Total hospital charges associated with every encounter during the perioperative period were obtained. RESULTS: Patient demographics, comorbidities, tumor metrics, and surgical characteristics were equivalent between groups. Postoperative wound complications, reoperations, readmissions, and disease-specific survival did not differ between cohorts. Costs associated with each reconstruction strategy were equivalent on bivariate and multivariate testing, when accounting for operating room time, hospital length of stay, and reoperation rate. CONCLUSIONS: Our study identifies no significant difference in patient outcome measures or cost between planned immediate and delayed flap reconstruction following STS resection. These results support the implementation of either treatment strategy in keeping with patient-centered, multidisciplinary care principles.

Centralized prostatectomy with intraoperative NeuroSAFE margin assessment improves surgical margin control.

AIMS: To investigate the surgical margin status in patients with prostate cancer who underwent robot-assisted radical prostatectomy (RARP) with intraoperative neurovascular structure-adjacent frozen-section analysis (NeuroSAFE) and evaluate differences compared to patients who underwent radical prostatectomy without NeuroSAFE. PATIENTS AND METHODS: Between September 2018 and January 2021, 962 patients underwent centralized RARP with NeuroSAFE. A secondary resection was performed in case of a positive surgical margin (PSM) on intraoperative frozen section (IFS) analysis to convert a PSM into a negative surgical margin (NSM). A retrospective cohort consisted of 835 patients who had undergone radical prostatectomy in a tertiary centre without NeuroSAFE between January 2000 and December 2017. We performed multivariable logistic regression to evaluate differences in risk of PSM between cohorts after controlling for clinicopathological variables. RESULTS: Patients operated with NeuroSAFE in the centralized clinic had 29% PSM at a definitive pathological RP examination. The median cumulative length of definitive PSM was 1.1 mm (interquartile range: 0.4-3.8). Among 275 men with PSM, 136 (49%) had a cumulative length ≤1 mm and 198 (72%) ≤3 mm. After controlling for PSA, Grade group, cribriform pattern, pT-stage, and pN-stage, patients treated in the centralized clinic with NeuroSAFE had significantly lower odds on PSM (odds ratio [OR]: 0.70, 95% confidence interval [CI]: 0.56-0.88; P = 0.002), PSM length >1 mm (OR: 0.14, 95% CI: 0.09-0.22; P < 0.001), and >3 mm (OR: 0.21, 95% CI: 0.14-0.30; P < 0.001). CONCLUSION: This study provides a detailed overview of surgical margin status in a centralized RP NeuroSAFE cohort. Centralization with NeuroSAFE was associated with lower PSM rates and significantly shorter PSM cumulative lengths, indicating improved control of surgical margin status.

Assessment of Noninferiority Margins in Cardiovascular Medicine Trials.

Background: Noninferiority trials are increasingly common in cardiovascular medicine, but their reporting and interpretation are challenging, particularly when an absolute risk difference is used as noninferiority margin. Objectives: This study aimed to investigate the effect of using absolute rather than relative noninferiority margins in cardiovascular trials. Methods: We reviewed noninferiority trials presented at major cardiovascular conferences from 2015 to 2022 and published within the same period. Based on the actual versus anticipated event rates in the control group, we recalculated the absolute noninferiority margin and re-assessed the trial results. The primary outcome of interest was the proportion of trials with a different interpretation after recalculation. Additionally, we analyzed the conclusion statements of these trials to determine if cautionary notes for the interpretation of study results were included. Results: We analyzed a total of 768 trials, of which 88 had a noninferiority design and 66 used an absolute noninferiority margin. Of 48 comparisons from 45 trials qualifying for the analysis, 11 (22.9%) had divergent results after recalculation of the absolute noninferiority margin based on the observed rather than anticipated event rate. Ten trials originally claiming noninferiority, did not meet it after the margin recalculation. All of them did not include statements suggesting cautionary interpretation of the study results in the conclusion section. Compared with the other trials, these displayed a larger median difference between anticipated and recalculated noninferiority margins (44.7% [IQR: 38.6%-56.7%] vs 15.3% [IQR: -1.5% to 28.9%]; P < 0.001). Conclusions: Recalculating noninferiority margins based on actual event rates, rather than anticipated ones, led to different outcomes in approximately 1 out of 4 cardiovascular trials, with most divergent trials lacking cautionary interpretation. These findings emphasize the importance of using or supplementing the relative noninferiority margin, particularly in studies with significant deviations between observed and expected event rates. This underscores the critical need for enhanced methodological and reporting standards in noninferiority trials, especially those employing absolute margins.

Evaluation of genetic consequences of stocking on the southern-margin populations of white-spotted charr.

Coldwater-adapted freshwater fishes, especially their populations along warm-range margins, are most vulnerable to the climate oscillations associated with global warming. Stocking is a major strategy for avoiding the extinction of these species. However, while stocking can reverse the decline of isolated populations, it may also result in a loss of genetic diversity in the native local population due to the introgressive replacement of hatchery genes. To plan an adequate strategy for conserving locally adapted populations, the genetic impacts of stocking on native lineages should be evaluated from small river branches to wide-ranging drainage areas. We investigated the population genetic structure of white-spotted charr (Salvelinus leucomaenis) within its southern range (Lake Biwa basin, Japan). By applying genome-wide SNP analysis to the population's genetic structure, we assessed the extent of genetic introgression resulting from stocking. White-spotted charr in the Lake Biwa watershed constitutes a distinctive genetic group, within which apparent genetic differentiation was observed. The hatchery-reared fish line commonly used for supplementation stocking in the catchment was discernable from the native population, enabling us to analyze genetic introgression across the entire drainage area. Admixed individuals resulting from hatchery introgression were observed in most of the stocked sites that showed relatively high heterozygosity and nucleotide diversity. However, their genetic differentiation was much lower than that of native populations. The supplementation history as well as the road availability contributed substantially to the introgression of hatchery genes. Populations with the native genetic structure remained in the upstream regions of the tested rivers. However, their heterozygosity and nucleotide diversity were low when compared with that of the populations with hatchery supplementation. Our results shed light on the genetic impacts of stocking on isolated native populations and suggest that conventional supplementation methods cannot preserve a unique biodiversity in the distribution margin.

Role of Imaging in Predicting the Deep Surgical Margin in Gingivobuccal Complex Cancers: A Pilot Study.

Cancers arising from the gingivobuccal complex are one of the most common types of cancer in the oral cavity and are associated with poor prognosis. Among the various prognostic factors, positive surgical margin is the most important one that can be controlled by the operating surgeon. The deep surgical margins for buccal mucosa cancers is normally assessed by palpating the skin for induration and skin pinchability. The present study evaluates the role of imaging in assessing the deep surgical margin and its efficacy for skin preservation in buccal mucosa/ gingivobuccal carcinomas. The patients of gingivobuccal complex squamous cell carcinomas after histopathological confirmation were selected for the study. In imaging, the distance between the base of the tumour and skin (epidermis) of the cheek was measured by a senior radiologist preoperatively. The frozen section findings were confirmed by histopathological examination and the depth of invasion of the tumour was measured and the clearance of the deep surgical margin was confirmed. The correlation between imaging, skin pinch test and histopathological examination of the specimen was assessed. The sensitivity and specificity of imaging to predict the skin preservation (deep surgical margin more than 5 mm) is 100% and 75% respectively compared to sensitivity and specificity of skin pinch test of 82.6% and 50% respectively. Imaging is an effective tool in predicting the skin preservation and skin excision compared to skin pinch test. Compared to the skin pinch test, imaging appears to be a useful tool for advising surgeons on skin preservation vs excision.

Time-dependent prognostic impact of circumferential resection margin in T3 thoracic esophageal squamous cell carcinoma.

Esophageal cancer presents a clinical challenge due to its high incidence and unfavorable prognosis. The prognostic role of the circumferential resection margin (CRM) remains highly controversial, potentially due to its temporal dynamics coupled with variability in follow-up durations across studies. We aimed to explore the time-dependent prognostic significance of CRM in T3 esophageal squamous cell carcinomas (ESCCs). We systematically reviewed literature from 1990 to 2023 to determine how follow-up duration influences the prognostic role of CRM in esophageal cancer. Concurrently, we performed a retrospective examination of 354 patients who underwent treatment at the National Cancer Center between 2015 and 2018. Integrating a time interaction term in the Cox regression analyses enabled us to not only identify independent risk factors affecting overall survival (OS) but also to specifically scrutinize the potential temporal variations in CRM's prognostic impact. Our literature review suggested that CRM's influence on prognosis diminishes with longer follow-up durations for both classifications, namely the Royal College of Pathologists (RCP) (ß = -0.003, P < 0.001) and the College of American Pathologists (CAP) (ß = -0.007, P < 0.001). Time-dependent multivariate Cox regression analysis emphasized the evolving nature of CRM's prognostic effect, and the inclusion of the time interaction term enhanced model accuracy. In conclusion, CRM is an independent prognostic factor for T3 thoracic ESCC patients. Its influence appears to decrease over extended follow-up periods, shedding light on the heterogeneity seen in previous studies. With the time interaction term, CRM becomes a more precise post-operative prognostic indicator for esophageal cancer.

Research on the Collision Risk of Fusion Operation of Manned Aircraft and Unmanned Aircraft at Zigong Airport.

Low-altitude airspace is developing rapidly, but the utilization rate of airspace resources is low. Therefore, in order to solve the problem of the safe operation of the fusion of large UAVs and manned aircraft in the same airspace, this paper analyzes the theoretical calculation of the collision risk of the fusion operation of manned aircraft and UAVs at Feng Ming Airport in Zigong, verifying that while assessing the safety spacing of 10 km in the lateral direction, it further simulates the possibility of calculating the theoretical smaller safety spacing. The study will propose a new theory of error spacing safety margin and improve it according to the traditional Event collision risk model, combining the error spacing safety margin to establish an improved collision model more suitable for the fusion operation of manned and unmanned aircraft and reduce the redundancy of calculation. The error factors affecting manned and unmanned aircraft at Zigong Airport are analyzed, and theoretical calculations are analyzed by combining the actual data of Zigong Airport. Finally, the Monte Carlo simulation method is used to solve the error, substitute the calculation results, and simulate a section of the trajectory of the fusion operation for the reverse argument. The theoretical calculation results show that the collision risk from 10 km to 8 km satisfies the lateral target safety level (TSL) specified by ICAO under both traditional and improved models. The collision risk calculated by the improved model incorporating the error spacing safety margin is smaller, which enhances the safety of the model calculations. The results of the study can provide theoretical references for the fusion operation of manned and unmanned aircraft.