Reference Markers Research Articles

Multidimensional Machine Learning for Assessing Parameters Associated With COVID-19 in Vietnam: Validation Study.

Machine learning (ML) is a type of artificial intelligence strategy. Its algorithms are used on big data sets to see patterns, learn from their results, and perform tasks autonomously without being instructed on how to address problems. New diseases like COVID-19 provide important data for ML. Therefore, all relevant parameters should be explicitly quantified and modeled. The purpose of this study was to determine (1) the overall preclinical characteristics, (2) the cumulative cutoff values and risk ratios (RRs), and (3) the factors associated with COVID-19 severity in unidimensional and multidimensional analyses involving 2173 SARS-CoV-2 patients. The study population consisted of 2173 patients (1587 mild status [mild group] and asymptomatic patients, 377 moderate status patients [moderate group], and 209 severe status patients [severe group]). The status of the patients was recorded from September 2021 to March 2022. Two correlation tests, relative risk, and RR were used to eliminate unbalanced parameters and select the most remarkable parameters. The independent methods of hierarchical cluster analysis and k-means were used to classify parameters according to their r values. Finally, network analysis provided a 3-dimensional view of the results. COVID-19 severity was significantly correlated with age (mild-moderate group: RR 4.19, 95% CI 3.58-4.95; P<.001), scoring index of chest x-ray (mild-moderate group: RR 3.29, 95% CI 2.76-3.92; P<.001; moderate-severe group: RR 3.03, 95% CI 2.4023-3.8314; P<.001), percentage of neutrophils (mild-moderate group: RR 3.18, 95% CI 2.73-3.70; P<.001; moderate-severe group: RR 3.32, 95% CI 2.6480-4.1529; P<.001), quantity of neutrophils (moderate-severe group: RR 3.15, 95% CI 2.6153-3.8025; P<.001), albumin (moderate-severe group: RR 0.46, 95% CI 0.3650-0.5752; P<.001), C-reactive protein (mild-moderate group: RR 3.4, 95% CI 2.91-3.97; P<.001), and ratio of lymphocytes (moderate-severe group: RR 0.34, 95% CI 0.2743-0.4210; P<.001). Significant inversion of correlations among the severity groups is important. Alanine transaminase and leucocytes showed a significant negative correlation (r=-1; P<.001) in the mild group and a significant positive correlation in the moderate group (r=1; P<.001). Transferrin and anion Cl showed a significant positive correlation (r=1; P<.001) in the mild group and a significant negative correlation in the moderate group (r=-0.59; P<.001). The clustering and network analysis showed that in the mild-moderate group, the closest neighbors of COVID-19 severity were ferritin and age. C-reactive protein, scoring index of chest x-ray, albumin, and lactate dehydrogenase were the next closest neighbors of these 3 factors. In the moderate-severe group, the closest neighbors of COVID-19 severity were ferritin, fibrinogen, albumin, quantity of lymphocytes, scoring index of chest x-ray, white blood cell count, lactate dehydrogenase, and quantity of neutrophils. This multidimensional study in Vietnam showed possible correlations between several elements and COVID-19 severity to provide clinical reference markers for surveillance and diagnostic management.

The TPA score (total psoas muscle area) is the best marker for preoperative measurement of pre-sarcopenia in pancreatic surgery.

Pre-sarcopenia, defined by the loss of muscle mass, is significantly associated with an increased risk of postoperative complications in digestive surgery, particularly pancreatic resection. The five predominant markers of sarcopenia are: psoas muscle area (TPA), intramuscular adipose tissue content (IMAC), Average Hounsfield Unit Calculation (HUAC), Skeletal Muscle Mass Index (MMI), and the ratio between visceral adipose tissue area and muscle surface area (VFA/TAMA). No standard reference marker has been determined. This retrospective cohort included patients who underwent pancreatic resection at the University Hospital of Angers between January 2008 and June 2017. The goal was to determine the marker that was most significantly associated with morbidity and mortality in pancreatic surgery. The secondary objective was to determine the characteristics of pre-sarcopenic patients. The TPA score is the most sensitive marker for identifying patients at highest risk for immediate complications (P=0.008), proving far more sensitive than MMI (P=0.02), HUAC (P=0.34), IMAC (P=1), or VFA/TAMA (P=0.42). Postoperative mortality was 3.3% (n=5), morbidity was 63.8% (n=97). Pre-sarcopenic patients, as identified by the TPA index had significantly more immediate complications (71.2% versus 49.5%, P=0.008), in particular, more gastroparesis (P=0.02) and pancreatic fistula (P=0.03). In patients requiring pancreatic surgery, the prevalence of pre-sarcopenia is high and seems to be associated with a greater risk of immediate postoperative complications. The TPA score seems to be the most sensitive marker for detecting pre-sarcopenia. Evaluation of TPA preoperatively would make it possible to identify priority patients a priori who might benefit from pre-habilitation programs.

A Guide to Gene-Centric Analysis Using TreeSAPP.

Gene-centric analysis is commonly used to chart the structure, function, and activity of microbial communities in natural and engineered environments. A common approach is to create custom ad hoc reference marker gene sets, but these come with the typical disadvantages of inaccuracy and limited utility beyond assigning query sequences taxonomic labels. The Tree-based Sensitive and Accurate Phylogenetic Profiler (TreeSAPP) software package standardizes analysis of phylogenetic and functional marker genes and improves predictive performance using a classification algorithm that leverages information-rich reference packages consisting of a multiple sequence alignment, a profile hidden Markov model, taxonomic lineage information, and a phylogenetic tree. Here, we provide a set of protocols that link the various analysis modules in TreeSAPP into a coherent process that both informs and directs the user experience. This workflow, initiated from a collection of candidate reference sequences, progresses through construction and refinement of a reference package to marker identification and normalized relative abundance calculations for homologous sequences in metagenomic and metatranscriptomic datasets. The alpha subunit of methyl-coenzyme M reductase (McrA) involved in biological methane cycling is presented as a use case given its dual role as a phylogenetic and functional marker gene driving an ecologically relevant process. These protocols fill several gaps in prior TreeSAPP documentation and provide best practices for reference package construction and refinement, including manual curation steps from trusted sources in support of reproducible gene-centric analysis. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Creating reference packages Support Protocol 1: Installing TreeSAPP Support Protocol 2: Annotating traits within a phylogenetic context Basic Protocol 2: Updating reference packages Basic Protocol 3: Calculating relative abundance of genes in metagenomic and metatranscriptomic datasets.

Novel QTL associated with Rhizoctonia solani Kühn resistance identified in two table beet × sugar beet F2:3 populations using a new table beet reference genome

AbstractThe necrotrophic fungus Rhizoctonia solani Kühn is a major concern for table beet (Beta vulgaris L. ssp. vulgaris) producers across the United States causing upward of 75% losses in severe instances. Thus far, there have been minimal efforts to incorporate host resistance to R. solani in table beet germplasm. To investigate the genetic control of R. solani resistance in table beet, we developed two mapping populations. Parents of the two populations were a Rhizoctonia‐susceptible table beet inbred W357A and a resistant sugar beet germplasm FC709‐2 (sugar beet resistance population, SBRP) and a Rhizoctonia‐resistant table beet inbred W364B and a susceptible sugar beet inbred FC901/C817 (table beet resistance population, TBRP). In Spring 2020, F2:3 families were evaluated for response to artificial inoculation with R. solani AG 2‐2 IIIB isolate R1 in replicated greenhouse experiments. This work also represents the first use of the W357B table beet reference genome, utilized here to align genotyping‐by‐sequencing reads to identify polymorphic markers. Using interval linkage mapping, we identified one quantitative trait locus (QTL) in each of the two populations, each accounting for 30% of the phenotypic variation. The QTL in both the SBRP and TBRP were found on chromosome 2 and contained several putative resistance genes in annotations of the Beta vulgaris and Arabidopsis thaliana genomes. This is the first report of a QTL on chromosome 2 for resistance to R. solani in B. vulgaris ssp. vulgaris and the first identification of QTL for disease resistance in table beet. The newly developed table beet reference genome and markers identified in this study may be of value for marker‐assisted selection in breeding for resistance to R. solani in both sugar beet and table beet breeding programs.

Diagnostic Accuracy of GATA6 Immunostaining in Sebaceous Tumors of the Skin

The accurate diagnosis of skin adnexal neoplasms is sometimes challenging but is necessary because medical management and follow-up may differ between tumors. GATA6 transcription factor has been identified as a new marker of the upper folliculosebaceous compartment (lower infundibulum, junctional zone and isthmus, and upper sebaceous gland) in the human skin. We aimed to determine the diagnostic accuracy of GATA6 immunostaining to diagnose sebaceous tumors compared with that to diagnose other adnexal and nonadnexal cutaneous neoplasms. We conducted a retrospective, evaluator-nonblinded study comparing the reference standard (diagnosis by an expert dermatopathologist) with GATA6 immunostaining to identify sebaceous tumors in a cohort containing 234 different tumors. The GATA6 expression score was significatively higher in sebaceous than that in nonsebaceous tumors. In addition, tumors originating from the upper hair follicle showed positive results for GATA6 staining; however, they showed lower GATA6 expression scores. Detection of sebaceous tumors using GATA6 positivity had a sensitivity of 95.7% (95% CI, 85.8-99.2), specificity of 80.8% (95% CI, 74.5-85.8), positive predictive value of 55.6% (95% CI, 44.7-65.9), and negative predictive value of 98.7% (95% CI, 95.4-99.8). GATA6 showed similar sensitivity to adipophilin, the reference marker; however, the specificity of GATA6 was higher, as observed in a cohort of 106 tumors enriched in squamous cell carcinomas with clear-cell histology. In addition, GATA6 positivity was assessed in 39 sebaceous carcinomas and compared with epithelial membrane antigen (EMA), CK7, and androgen receptor (AR) staining results. Although CK7 staining displayed lower diagnostic performances, GATA6 staining showed comparable results as EMA and AR. Finally, we found GATA6 expression in skin metastases of gastrointestinal origin, whereas GATA6 was absent in metastases originating from breast or lung cancers. Overall, our work identified GATA6 immunostaining as a new diagnostic tool for sebaceous tumors.

Evaluating Changes in Apparent Chord Mu after Pharmacological Pupil Dilatation

Introduction: Preoperative measurements of apparent chord mu length above 0.6 mm have been associated with higher risks for photic phenomena after cataract surgery with multifocal intraocular lenses (MFIOLs). Methods: This retrospective study evaluated patients scheduled for elective cataract surgery at a single tertiary medical center between 2021 and 2022. Pupil diameter and apparent chord mu length were analyzed for eyes with biometry measurements from IOLMaster 700 (Carl Zeiss Meditec, AG) under photopic light conditions, before and after pharmacological pupil dilatation. Exclusion criteria were visual acuity worse than 20/100, prior intraocular surgery, refractive surgery, iris-related procedures, or pupil abnormalities affecting dilatation. Apparent chord mu lengths before and after pupil dilatation were compared. In addition, multivariate linear regression analysis, using a stepwise method, was conducted to assess possible predictors of apparent chord values. Results: Included were 87 eyes of 87 patients. Mean chord mu length increased after pupillary dilatation from 0.32 ± 0.17 mm to 0.41 ± 0.17 mm for right eyes (p < 0.001) and from 0.29 ± 0.16 mm to 0.40 ± 0.22 mm for left eyes (p < 0.001). Seven eyes (8.0%) had an apparent chord mu of 0.6 mm and above pre-dilatation. Fourteen eyes (16.1%) with an apparent chord mu under 0.6 mm pre-dilatation had apparent chord mu of 0.6 mm or above post-dilatation. Conclusion: Apparent chord mu length significantly increases after pharmacological pupillary dilatation. Pupil size and dilatation status should always be considered during patient selection for a planned MFIOL using apparent chord mu length as a reference marker.

Application of three-dimensional reconstruction in stomatology

Three-dimensional reconstruction (3D) in computer vision, is the process of three-dimensional view information from single or multiple views. In medicine, 3D reconstruction techniques are mainly based on MSCT, magnetic resonance imagin and other output medical digital image communication protocol (DICOM) format files. As a new digital medical technology, 3D reconstruction technology has been widely used in the field of stomatology, using 3D software, we can freely rotate, segment and view the CT scan results from many different angles, so that we can get more clear skull contrast and more information, data in CT scan results can also be processed so that reference markers can be clearly displayed for better diagnosis and treatment [1]. It has the unique preoperation design advantage, reduces the operation time, enhances the operation accuracy.

Artifacts Can Be Deceiving: The Actual Location of Deep Brain Stimulation Electrodes Differs from the Artifact Seen on Magnetic Resonance Images

Introduction: Deep brain stimulation (DBS) is a common treatment for a variety of neurological and psychiatric disorders. Recent studies have highlighted the role of neuroimaging in localizing the position of electrode contacts relative to target brain areas in order to optimize DBS programming. Among different imaging methods, postoperative magnetic resonance imaging (MRI) has been widely used for DBS electrode localization; however, the geometrical distortion induced by the lead limits its accuracy. In this work, we investigated to what degree the difference between the actual location of the lead’s tip and the location of the tip estimated from the MRI artifact varies depending on the MRI sequence parameters such as acquisition plane and phase encoding direction, as well as the lead’s extracranial configuration. Accordingly, an imaging technique to increase the accuracy of lead localization was devised and discussed. Methods: We designed and constructed an anthropomorphic phantom with an implanted DBS system following 18 clinically relevant configurations. The phantom was scanned at a Siemens 1.5 Tesla Aera scanner using a T₁MPRAGE sequence optimized for clinical use and a T₁TSE sequence optimized for research purposes. We varied slice acquisition plane and phase encoding direction and calculated the distance between the caudal tip of the DBS lead MRI artifact and the actual tip of the lead, as estimated from MRI reference markers. Results: Imaging parameters and lead configuration substantially altered the difference in the depth of the lead within its MRI artifact on the scale of several millimeters − with a difference as large as 4.99 mm. The actual tip of the DBS lead was found to be consistently more rostral than the tip estimated from the MR image artifact. The smallest difference between the tip of the DBS lead and the tip of the MRI artifact using the clinically relevant sequence (i.e., T₁MPRAGE) was found with the sagittal acquisition plane and anterior-posterior phase encoding direction. Discussion/Conclusion: The actual tip of an implanted DBS lead is located up to several millimeters rostral to the tip of the lead’s artifact on postoperative MR images. This distance depends on the MRI sequence parameters and the DBS system’s extracranial trajectory. MRI parameters may be altered to improve this localization.

Prognostic value of KRAS subtype in patients with PDAC undergoing radical resection.

To explore the frequency distribution of KRAS mutant subtypes in patients with resectable PDAC in China and then evaluate the prognostic value of different KRAS subtypes in patients with PDAC undergoing radical resection. The clinicopathological data and gene test reports of 227 patients undergoing PDAC radical surgery at Hunan Provincial People's Hospital from 1 January 2016 to 1 January 1 2020 were retrospectively evaluated. There were 118 men (52%) and 109 women (48%). The mean age was 58.8 ± 10.3 years. After univariate analysis of the clinicopathological factors (sex, age, presence or absence of underlying disease, location of the primary tumour, tumour TNM stage, T stage, N stage, presence or absence of vascular invasion, presence or absence of nerve invasion, surgical margin, KRAS mutation subtype), variables with P < 0.1 were included in the multivariate Cox regression model analysis, and the log-rank sum test and Kaplan-Meier curves were used to assess the correlation of the KRAS mutation subtype with the overall survival time. KRAS mutations were detected in 184 of 227 patients (81.1%) (G12D: 66; G12V: 65; G12R: 27; Q61:26) and were not detected in 43 patients (18.9%). KRAS mutations were associated with tumour differentiation (P = 0.001), TNM stage (P = 0.013), and T stage (P < 0.001). Multivariate Cox regression model analysis showed that N stage, surgical margin, tumour differentiation, and KRAS-G12D mutation were independent prognostic factors for DFS and OS. Patients with the KRAS-G12D subtype had shorter OS with a median OS of 12 months (HR: 0.55, CI: 0.39-0.77, P < 0.001), and patients with KRAS wild-type had longer OS with a median OS of 19 months (HR: 0.57, CI: 0.42-0.76, P < 0.001). KRAS wild-type individuals are more prevalent in the Chinese population than in European or American populations. Patients undergoing surgery had a reduced percentage of tumors with KRAS-G12D. When determining the prognosis of individuals with radically resected PDAC, reference markers for KRAS mutation subtypes can be employed.

The Reibergram for immunoglobulin A in dogs: Evaluation of intrathecal IgA synthesis using a quotient graph in dogs with neurological diseases.

Increased cerebrospinal fluid (CSF) protein concentration is a common finding in neurological diseases of dogs. Distinguishing between intrathecally-produced proteins and proteins that have passed the blood-CSF barrier because of barrier disruption facilitates diagnosis. Albumin is a microprotein mainly produced extrathecally that can be used as a reference marker for blood-CSF barrier dysfunction. Develop a quotient graph based on the CSF/serum quotient of albumin and immunoglobulin A (IgA; Reibergram) to visualize intrathecal IgA synthesis and blood-CSF barrier dysfunction. Retrospective single-center cohort study. A hyperbolic function was developed using data from 6 healthy Beagles and 38 dogs with neurological diseases in which an isolated blood-CSF barrier dysfunction was expected. The function was validated using data from 10 dogs with expected intrathecal IgA synthesis and was visualized as a quotient graph. Finally, the graph was used to evaluate data of 118 dogs with various neurological diseases. Within the Reibergram, the function describes the upper values of physiological IgA quotients. It detects diseases with expected intrathecal IgA synthesis with higher sensitivity (85%) and specificity (89%) than the IgA index. The upper value of the physiological albumin quotient is 2.22 and detects diseases with expected blood-CSF barrier dysfunction (sensitivity: 81%; specificity: 88%). The canine Reibergram can detect blood-CSF barrier dysfunction and intrathecal IgA synthesis in the majority of cases. The graphical visualization simplifies data evaluation and makes it a feasible tool in routine CSF diagnostic testing.

Optimization strategies for mitigating nitrogen loss in the aerobic composting of pig manure and microbial changes revealed by metagenomic analysis

In this research, comprehensive optimization strategies for mitigating nitrogen loss in pig manure compost was screened out and nitrogen cycle microbial changes revealed by metagenomic technology. Results showed the optimum combination of process conditions as C/N ratio of 25, turning frequency of twice/day, addition of biochar and inoculation with nitrogen retaining microbial agent. The nitrogen loss rate of the optimized group was 14.67%, which was 45.33% significantly lower than that of the traditional group. NH3, N2O, and NO emission significantly decreased by 42.74%, 48.93%, and 69.95%. Metagenomic analysis revealed that process optimization could change the microbial community, functional genes and metabolism pathways of the nitrogen cycling in the composting process. Nitrogen loss was mainly mitigated by increasing the enzyme activities in nitrogen assimilation (increased by 11.80%), nitrification (increased by 39.35%), and nitrogen fixation pathways (increased by 74.72%) and reducing the enzyme activities in denitrification pathways (decreased by 35.20%). The findings provided reference markers for further exploration of compost nitrogen loss. This comprehensive optimization strategies method for mitigating nitrogen loss was recommended in aerobic composting of pig manure.

Microsatellite analysis and polymorphic marker development based on the full-length transcriptome of Camellia chekiangoleosa

Camellia chekiangoleosa is a popular variety of Oil-camellia that has high oil production and ornamental value. Microsatellite (SSR) markers are the preferred tool for the molecular marker-assisted breeding of C. chekiangoleosa. By focusing on the problems of the low development efficiency of polymorphic SSR markers and the lack of available functional markers in Oil-camellia, we identified 97,510 SSR loci based on the full-length transcriptome sequence of C. chekiangoleosa. An analysis of SSR characteristics showed that mononucleotide (51.29%) and dinucleotide (34.36%) SSRs were the main repeat types. The main SSR distribution areas based on proportion covered were ordered as follows: 5'UTR > 3'UTR > CDS. By comparing our data with those in databases such as GO and KEGG, we obtained functional annotations of unigene sequences containing SSR sites. The data showed that the amplification efficiency of the SSR primers was 51.72%, and the development efficiency of polymorphic SSR primers was 26.72%. Experiments verified that dinucleotide and pentanucleotide SSRs located in UTR regions could produce more polymorphic markers. An investigation into the genetic diversity of several C. chekiangoleosa populations also suggested that the developed SSR markers had higher levels of polymorphism. This study will provide a reference and high-quality markers for the large-scale development of functional SSR markers and genetic research in Oil-camellia.

Kirschner Wire as a Reference Marker for the Positioning of a Syndesmotic Screw: A Radiological Study and Clinical Evaluation.

No consensus has been reached regarding optimal implantation for a syndesmotic screw. Thus, we aimed to explore the feasibility of a reliable and static fibular incisura plane reference for ideal syndesmotic screw placement. A retrospective review of computed tomography (CT) scans of 42 uninjured adult ankles with foot fractures were analyzed to measure the tibiofibular vertical distance (TFVD) at 2.5 cm proximal to the plafond from August 2016 to June 2017 in our hospital. The patients (20 females, 22 males) were divided into four groups according to their TFVD: 0-1, 1-2, 2-3, and 3-4 mm, and patients in each group were counted. We retrospectively assessed 41 patients (15 females, 26 males) who underwent syndesmotic screw fixation for ankle fractures from December 2015 to June 2020. We performed t-testing of two independent samples to determine the differences in the angle between the anatomic axis of the syndesmosis and screw axis (AAS) and ankle function using the American Orthopaedic Foot and Ankle Society (AOFAS) score at 3 and 6 months postoperatively between the conventional (20 patients) and K-wire marker (21 patients) groups. The correlation between the AAS and AOFAS score was analyzed. The TFVD measured 2.23 ± 1.01 mm at 2.5 cm proximal to the plafond, and occurred at 25% of the distance from 2 to 3 mm in 47.6% of the patients. This new technique decreased AAS deformation by 62%, from 13.01° ± 2.84° to 4.89° ± 2.43°, in the conventional group (p<0.001). At 3 months postoperatively, the AOFAS scores of ankle function were similar in both groups, but it was significantly better in the new group than that of conventional group at the 6-month follow-up (p=0.024). There was a moderate negative correlation between AAS and AOFAS score at 6 months postoperatively (R=-0.684). No obvious complications affecting ankle function were observed in either group postoperatively. Surgeons can accurately place a screw trajectory using the fibular incisura plane as a reliable intraoperative reference. A 1.6-mm K-wire placed in the syndesmosis at 2.5 cm proximal to the tibial plafond could act as a static marker of the syndesmotic plane.

S410 Algorithm Training and Independent Test Set Performance for a Molecular Non-Endoscopic Test for Detection of Esophageal Adenocarcinoma and Barrett’s Esophagus in Multicenter Cohorts

Introduction: Sedated endoscopy for Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC) detection is invasive and expensive. Non-endoscopic BE/EAC detection tools have been guideline-endorsed to facilitate higher patient participation at lower cost. We previously described a promising panel of 5 methylated DNA markers (MDMs) assayed on esophageal specimens obtained by a sponge-on-a-string (SOS) cell collection device in phase II studies. We aimed to train an algorithm (establishing marker cut offs, to adjudicate samples as positive/negative) using a final MDM panel followed by testing in an independent sample set. Methods: Algorithm training samples (N=352) were prospectively collected from patients seen at 6 US medical centers. Test samples (N=125) were obtained from an independent, NIH-funded study conducted at 3 US medical centers. Cases had columnar metaplasia with intestinal metaplasia; controls had no endoscopic evidence of BE. Histology was reviewed by expert GI pathologists. The SOS device (25 mm, 10 ppi) was swallowed and withdrawn after 6-8 minutes followed by criterion standard endoscopy within 24 hours. DNA was extracted and bisulfite treated. Five MDMs were blindly assayed using the long probe quantitative amplified signal method. The algorithm was set using cross-validated logistic regression. The locked algorithm was applied to assay results from the test set. Results: Baseline characteristics of patients in training and test sets were comparable (Table). The final panel included 3 MDMs (NDRG4, VAV3, and ZNF682) and a reference marker (B3GALT6). Overall sensitivity for BE/EAC detection in the training set was 81% (95% CI 76-88%) at 90% (85-94%) specificity. Overall BE/EAC sensitivity in the test set was 88% (78-94%) at 84% (70-93%) specificity. Sensitivity for HGD and EAC was 100% in the training and test sets. Sensitivity for short segment NDBE in the test set was 63% (38-84%). Areas under the receiver operating characteristic (AUROC) curve for BE/EAC detection were 0.92 (95% CI 0.89-0.95) and 0.94 (0.90-0.98) in the training and test sets, respectively (Figure). The algorithm was not influenced by age, sex, or smoking history. 97% of participants in the training set and 85% in the test set successfully swallowed the SOS device, which was well tolerated and safe. Conclusion: A 3-MDM panel for BE/EAC detection demonstrated excellent sensitivity for high risk BE cases in multi-center case control training and test sets.Figure 1.: Area under the receiver operating characteristics curves for a 3-marker methylated DNA panel assayed from cytology specimen extracted DNA in training and test sets. Table 1. - Baseline characteristics of patients and performance characteristics of SOS test (overall sensitivity and specificity, and stratified by BE dysplasia grade) in training and test sets Variable Training Set (N=198 controls,154 cases) Test Set(N= 44 controls,81 cases) P value (comparing training and test sets) Control Case Control Case Mean (SD) age 55 (13) 65 (10) 52 (15) 65 (11) 0.312 Male Sex (%) 102 (52) 119 (77) 17 (39) 64 (79) 0.992 Mean (SD) BMI 29 (7) 30 (6) 30 (7) 30 (6) 0.283 Ever Smokers % 77 (39) 87 (56) 18 (41) 47 (58) 0.733 Mean *SD) BE length, cm - 4 (3) - 5 (3) 0.070 Long segment BE, N, (%) - 97 (63) - 56 (69) 0.426 Short segment BE, N (%) - 57 (37) - 25 (31) BE dysplasia grade, N (%) EAC - 12 (8) - 2 (2) HGD - 18 (12) - 11 (14) LGD - 7 (4) - 10 (12) IND - 18 (12) - 14 (17) NDBE (long segment) - 57 (37) - 25 (31) NDBE (short segment) - 42 (27) - 19 (24) Training Set% Positive (95% CI) Test Set% Positive (95% CI) Overall 81% (76-88%) 88 (78-94) Dysplasia grade EAC 100 (100-100) 100 (16-100) HGD 100 (100-100) 100 (72-100) LGD 71 (0-100) 90 (55-100) IND 74 (0-100) 93 (66-100%) NDBE (long segment) 91 (73-100) 96 (80-100%) NDBE (short segment) 61 (25-100) 63 (38-84%) Control (No BE) 10 (2-21) 16 (7-30)

Augmented reality in minimally invasive spine surgery: early efficiency and complications of percutaneous pedicle screw instrumentation

Augmented reality (AR) employs an optical projection directly onto the user's retina, allowing complex image overlay on the natural visual field. In general, pedicle screw accuracy rates have improved with increasingly use of technology, with navigation-based instrumentation described as accurate in 89%-100% of cases. Emerging AR technology in spine surgery builds upon current spinal navigation to provide 3-dimensional imaging of the spine and powerfully reduce the impact of inherent ergonomic and efficiency difficulties. This publication describes the first known series of in vivo pedicle screws placed percutaneously using AR technology for MIS applications. After IRB approval, 3 senior surgeons at 2 institutions contributed cases from June, 2020 - March, 2022. 164 total MIS cases in which AR used for placement of percutaneous pedicle screw instrumentation with spinal navigation were identified prospectively. 155 (94.5%) were performed for degenerative pathology, 6 (3.6%) for tumor and 3 (1.8%) for spinal deformity. These cases amounted to a total of 606 pedicle screws; 590 (97.3%) were placed in the lumbar spine, with 16 (2.7%) thoracic screws placed. Patient demographics and surgical metrics including total posterior construct time (defined as time elapsed from preincision instrument registration to final screw placement), clinical complications and instrumentation revision rates were recorded in a secure and de-identified database. The AR system used features a wireless headset with transparent near-eye display which projects intra-operative 3D imaging directly onto the surgeon's retina. After patient positioning, 1 percuntaneous and 1 superficial reference marker are placed. Intra-operative CT data is processed to the headset and integrates into the surgeon's visual field creating a "see-through" 3D effect in addition to 2D standard navigation images. MIS pedicle screw placement is then carried out percutaneously through single line of sight using navigated instruments. Time elapsed from registration and percutaneous approach to final screw placement averaged 3 minutes and 54 seconds per screw. Analysis of the learning curve revealed similar surgical times in the early cases compared to the cases performed with more experience with the system. No instrumentation was revised for clinical or radiographic complication at final available follow-up ranging from 6-24 months. A total of 3 screws (0.49%) were replaced intra-operatively. No clinical effects via radiculopathy or neurologic deficit postoperatively were noted. This is the first report of the use of AR for placement of spinal pedicle screws using minimally invasive techniques. This series of 164 cases confirmed efficiency and safety of screw placement with the inherent advantages of AR technologies over legacy enabling technologies.

Composition and Bioactivity of a Modified Huang-Lian-Jie-Du Decoction.

Background Epidermal growth factor receptor inhibitors (EGFRIs) and tyrosine kinase inhibitors (TKIs) are key drugs in targeted cancer therapy. However, they may cause skin toxicity. We previously prepared a modified Huang-Lian-Jie-Du (mHLJD) decoction cream using 10 herbs, which effectively alleviated EGFRI/TKI-induced skin toxicity. In the present study, we identified the reference markers of the mHLJD decoction and investigated the anti-inflammatory and antibacterial effects of the mHLJD decoction extract. Methods We performed high-performance liquid chromatography (HPLC) to determine the composition of the mHLJD decoction. Human epidermoid A431 cells were treated with tumor necrosis factor (TNF)-α to induce inflammation; then, the effects of the mHLJD decoction extract on the cytokine expression were determined using a cytokine array and by performing real-time quantitative polymerase chain reaction (qPCR). The antibacterial effects of the extract were examined using disk diffusion and microdilution assays. Results HPLC results revealed that the mHLJD decoction primarily consisted of geniposide, berberine chloride, baicalin, coptisine, and palmatine. TNF-α treatment increased the expression of certain cytokines, including IL-1β, IL-8, M-CSF, and TGF-β2; however, pretreatment with the mHLJD decoction extract reduced their expression. The qPCR results demonstrated a decreased mRNA expression of IL-8, M-CSF, and TGF-β2. The antibacterial assay revealed that the extract exerted inhibitory effects on Staphylococcus aureus, forming an inhibition zone at the minimum inhibitory concentrations of 3.125 and 6.25 mg/mL; however, the extract exerted no effects on Escherichia coli and Pseudomonas aeruginosa. Conclusions. We developed an HPLC method to quantify the reference markers of the mHLJD decoction. The bioactivity analysis provided the potential mechanisms underlying the effects of the mHLJD decoction on EGFRI/TKI-induced skin toxicity.

An Experimental Study of a 3D Bone Position Estimation System Based on Fluoroscopic Images.

To compare a 3D preoperative planning image and fluoroscopic image, a 3D bone position estimation system that displays 3D images in response to changes in the position of fluoroscopic images was developed. The objective of the present study was to evaluate the accuracy of the estimated position of 3D bone images with reference to fluoroscopic images. Bone positions were estimated from reference points on a fluoroscopic image compared with those on a 3D image. The four reference markers positional relationships on the fluoroscopic image were compared with those on the 3D image to evaluate whether a 3D image may be drawn by tracking positional changes in the radius model. Intra-class correlations coefficients for reference marker distances between the fluoroscopic image and 3D image were 0.98–0.99. Average differences between measured values on the fluoroscopic image and 3D bone image for each marker corresponding to the direction of the bone model were 1.1 ± 0.7 mm, 2.4 ± 1.8 mm, 1.4 ± 0.8 mm, and 2.0 ± 1.6 mm in the anterior-posterior view, ulnar side lateral view, posterior-anterior view, and radial side lateral view, respectively. Marker positions were more accurate in the anterior-posterior and posterior-anterior views than in the radial and ulnar side lateral views. This system helps in real-time comparison of dynamic changes in preoperative 3D and intraoperative fluoroscopy images.

Significance of detecting the levels of miR-29a, survivin and interferon gamma release assay in patients with lung cancer and tuberculosis.

When lung cancer is combined with concurrent tuberculosis (TB), it increases the difficulty of diagnosis and treatment, leading to missed and/or misdiagnosed cases. To provide reference markers for the clinical diagnosis of patients with lung cancer complicated by active pulmonary TB (APT). The concentration of survivin in diseased tissue, and miR-29a and IGRAs interferon gamma (IFN-γ) in serum were evaluated in 25 patients with non-small cell lung carcinoma (NSCLC) complicated by APT, 32 patients with NSCLC and 30 patients with APT. The expression of miR-29a in serum of patients with APT was higher than in patients with NSCLC complicated by APT (least significant difference (LSD)-t = 4.724, p < 0.001), and the NSCLC group (LSD-t = 6.619, p < 0.001). Furthermore, patients with NSCLC complicated by APT had higher miR-29a concentration than the NSCLC group. The rate of positive survivin expression in NSCLC (χ2 = 23.418, p < 0.001) and NSCLC combined with APT group (χ2 = 17.160, p < 0.001) was significantly higher than in patients with APT. The concentration of IFN-γ in serum of the NSCLC complicated by APT group (LSD-t = 2.912, p = 0.004) and the APT group (LSD-t = 4.452, p < 0.001) was higher than in the NSCLC group. The level of IFN-γ in serum of the NSCLC complicated by APT group were higher than in the APT group, but there was no statistical difference. The levels of MiR-29a, Survivin and IFN-γ was helpful for differential diagnosis of lung cancer and tuberculosis.

Non-invasive blood glucose sensing by machine learning of optic fiber-based speckle pattern variation.

.SignificanceThe ability to perform frequent non-invasive monitoring of glucose in the bloodstream is very applicable for diabetic patients.AimWe experimentally verified a non-invasive multimode fiber-based technique for sensing glucose concentration in the bloodstream by extracting and analyzing the collected speckle patterns.ApproachThe proposed sensor consists of a laser source, digital camera, computer, multimode fiber, and alternating current (AC) generated magnetic field source. The experiments were performed using a covered (with cladding and jacket) and uncovered (without cladding and jacket) multimode fiber touching the skin under a magnetic field and without it. The subject’s finger was placed on a fiber to detect the glucose concentration. The method tracks variations in the speckle patterns due to light interaction with the bloodstream affected by blood glucose.ResultsThe uncovered fiber placed above the finger under the AC magnetic field (150 G) at 140 Hz was found to have a lock-in amplification role, improving the glucose detection precision. The application of the machine learning algorithms in preprocessed speckle pattern data increase glucose measurement accuracy. Classification of the speckle patterns for uncovered fiber under the AC magnetic field allowed for detection of the blood glucose with high accuracy for all tested subjects compared with other tested configurations.ConclusionsThe proposed technique was theoretically analyzed and experimentally validated in this work. The results were verified by the traditional finger-prick method, which was also used for classification as a conventional reference marker of blood glucose levels. The main goal of the proposed technique was to develop a non-invasive, low-cost blood glucose sensor for easy use by humans.

Ideal entry point and trajectory for C2 pedicle screw placement in children: a 3D computed tomography study.

To identify the ideal entry point for pediatric C2 pedicle screw and to obtain parameters of it for the indication of pediatric atlantoaxial fusion arthrodesis. The pediatric cervical CT images were reconstructed into the 3D digital models and the C2 vertebrae were separated. The location of ideal entry point and screw placement related linear and angular parameters were assessed on the 3D digital models. A total of 214 pedicles from 107 C2 digital models were analyzed. The average entry point for C2 was 3.80 ± 2.78mm medial to the lateral notch (LN) and 2.57 ± 1.70mm superior to the LN. The average pedicle diameter (PD) was 6.02 ± 1.31mm, and the average pedicle screw length (PSL) was 25.63 ± 3.46mm. Statistical differences were found between different sex for PD and PSL (P < 0.05). As patient age increases, using the most lateral and inferior edge of the lateral mass as a reference marker, the entry point tends to move medial and cephalad, when using the LN as a reference marker, the entry point tends to move medial and slightly caudad. Univariate linear regression analysis suggested that these linear parameters were associated with age (P < 0.01). In this study, we found that the measurement results of C2 pedicle screw varied based on sex, laterality, and ages for children younger than 18years. The entry point of the screws facilitating ideal trajectory tends to change in a linear way as a function of age. This information helps the surgeon to establish the specific anatomy related to C2 pedicle screw placement to facilitate fixation in the pediatric patients.