Initial Specimen Research Articles

In vitro assessment of effect of initial specimen diversion device on detection of central venous catheter contamination or colonization.

The role of initial specimen diversion devices (ISDDs) in preventing contamination of central venous catheter (CVC) blood cultures is undefined. A model to simulate CVC colonization and contamination compared standard cultures with ISDD technique. ISDD detected 100% of colonized CVCs while decreasing false-positive cultures from 36% to 16%.

Performance of Ultrasensitive Polymerase Chain Reaction Testing for JC Polyomavirus in Cerebrospinal Fluid Compared with Pathological Diagnosis of Progressive Multifocal Leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease caused by the JC polyomavirus (JCPyV). Based on the clinical criteria, PML is diagnosed via polymerase chain reaction (PCR) detection of JCPyV DNA in cerebrospinal fluid (CSF) in combination with neurological and imaging findings. Although the utility of CSF JCPyV testing using ultrasensitive PCR assays has been suggested, its potential requires further evaluation. This study retrospectively analyzed the detection performance of ultrasensitive PCR for CSF JCPyV in patients who underwent brain tissue examination based on the pathological diagnostic criteria for PML. Of the 110 patients with pathologically confirmed definite PML or not PML, standard and ultrasensitive CSF testing was performed for 36 and 74 patients, respectively. The sensitivity of ultrasensitive CSF JCPyV testing of the initial specimens was 85%. With the addition of the follow-up testing, this figure increased to 95%. The specificity and false-positive rate of ultrasensitive CSF JCPyV testing, including follow-up, were 100% and 0%, respectively. No statistically significant correlation was observed between CSF and brain JCPyV levels. The results of this study demonstrate the high sensitivity and accuracy of ultrasensitive CSF JCPyV testing and provide essential information for the clinical diagnosis of PML.

Do blood contamination reduction devices work? A single institution comparison.

We compare two initial specimen diversion devices evaluated over 3 months to investigate their utility in lowering blood culture contamination rates at or below 1%. Overall contamination rates during trial periods were 2.46% and 2.60% but usage was low, whereas device-specific contamination rates were 0.68% and 0.8%, respectively.

Longitudinal multimodal profiling of IDH-wildtype glioblastoma reveals the molecular evolution and cellular phenotypes underlying prognostically different treatment responses.

Despite recent advances in the biology of IDH-wildtype glioblastoma, it remains a devastating disease with median survival of less than 2years. However, the molecular underpinnings of the heterogeneous response to the current standard-of-care treatment regimen consisting of maximal safe resection, adjuvant radiation, and chemotherapy with temozolomide remain unknown. Comprehensive histopathologic, genomic, and epigenomic evaluation of paired initial and recurrent glioblastoma specimens from 106 patients was performed to investigate the molecular evolution and cellular phenotypes underlying differential treatment responses. While TERT promoter mutation and CDKN2A homozygous deletion were early events during gliomagenesis shared by initial and recurrent tumors, most other recurrent genetic alterations (eg, EGFR, PTEN, and NF1) were commonly private to initial or recurrent tumors indicating acquisition later during clonal evolution. Furthermore, glioblastomas exhibited heterogeneous epigenomic evolution with subsets becoming more globally hypermethylated, hypomethylated, or remaining stable. Glioblastoma that underwent sarcomatous transformation had shorter interval to recurrence and were significantly enriched in NF1, TP53, and RB1 alterations and the mesenchymal epigenetic class. Patients who developed somatic hypermutation following temozolomide treatment had significantly longer interval to disease recurrence and prolonged overall survival, and increased methylation at 4 specific CpG sites in the promoter region of MGMT was significantly associated with this development of hypermutation. Finally, an epigenomic evolution signature incorporating change in DNA methylation levels across 347 critical CpG sites was developed that significantly correlated with clinical outcomes. Glioblastoma undergoes heterogeneous genetic, epigenetic, and cellular evolution that underlies prognostically different treatment responses.

Implementation of an initial specimen blood culture diversion device to reduce blood culture contamination: lessons learned.

Implementation of an initial specimen blood culture diversion device to reduce blood culture contamination: lessons learned.

Illustration of the Financial Impact of Usage of Initial Specimen Diversion Devices (ISDD) or Continued Educational Initiatives on the Costs from Blood Culture Contamination

Abstract Introduction/Objective Blood culture contamination (BCC) has the potential to lead to additional healthcare system costs and harm to patient. Two ways to reduce BCC have been explored in the literature and are economically modeled including initial specimen diversion devices (ISDD) and continued education on phlebotomy. Methods/Case Report A literature review on the economic costs of BCC, ISDD efficacy, and phlebotomy education to reduce BCC rates was undertaken. The reported average BCC at a veteran affairs medical center (VAMC), its reported rate during a month of phlebotomy training, the cost of an ISDD device at VAMC, and the average wage for 4 hours of phlebotomy manager time for training was noted. An illustrative economic model involving 100 patients was used at BCC rates of 1%, 2%, and 3% along with what had been observed at the VAMC was used for economic modeling. Results (if a Case Study enter NA) It was previously reported by Skoglund et al that in laboratories with rapid diagnostic testing modalities (such as MALDI-TOF or PCR testing), the cost per BCC event is $13,026 versus $8,287 in costs for a negative blood culture. ISDD efficacy in the literature reviewed (74.1% to 87.5%), continuous education efficacy (16.2% to 57.8%), ISDD device cost ($17.70 per device), and the hourly wage of a phlebotomy supervisor ($29.34) were noted. The reported average BCC rate from a regional VAMC was 1.33%, and during the month with education, the rate was 0.5%. From a model of 100 patients, ISDD device savings ranged from $1,741.60-$2,376.63 (1% BCR), $5,253.20-$6,523.25 (2% BCR), and $8,764.79-$10,669.88 (3% BCR). Education savings ranged from $755.98-$2,727.41 (1% BCR), $1,523.70-5,466.55 (2% BCR), and $2,291.42-$8,205.69 (3% BCR). The observed impact of education at the regional VAMC would have resulted in savings of $650.83 per 100 patients. Conclusion Both education and ISDD devices can result in significant savings from the costs of BCC.

Epigenetic Characteristics in Primary and Recurrent Glioblastoma-Influence on the Clinical Course.

Epigenetic tumor characteristics are in focus for glioblastoma prognosis. This raises the question if these characteristics present with stable expression during the progression of the disease, and if potential temporal instability might influence their prognostic value. A total of 44 patients suffering from glioblastoma who were treated for their primary and relapse tumors were included in the study. Tumor specimens from the initial and recurrent tumor resection were subjected to evaluation of MGMT, p15, and p16 methylation statuses. MiRNA-21, -24, -26a, and -181d expression was evaluated as well. The stability of these epigenetic markers during the progression of the disease was correlated with further clinical data. A Cancer Genome Atlas (TCGA) dataset of 224 glioblastoma patients was used as an independent cohort to validate the results. Instability was observed in all examined epigenetic markers. MGMT methylation changed in 30% of patients, p15 methylation changed in 35%, and p16 methylation changed in 37.5% of cases. MiRNA expression in corresponding initial and relapse tumor specimens varied considerably in general, individual cases presented with a stable expression. Patients with a decreased expression of miRNA-21 in their recurrence tumor showed significantly longer overall survival. These results are supported by the data from TCGA indicating similar results. Epigenetic characteristics may change during the course of glioblastoma disease. This may influence the prognostic value of derived molecular markers.

Monkeypox pandemic in Sudan, surveillance epidemiologic report, 2022

BackgroundMpox, is a zoonosis that is known to be endemic in several Central and West African countries. Recently, in 2022, it has emerged in Europe and United States, what raised the alarm to be declared in late June 2024 as a public health event of international concern. This study aimed to give insight about the recent spread of mpox in Sudan, and documents the epidemiologic situation.MethodsThrough a cross-sectional design, Sudan mpox data was extracted from the disease surveillance line-list at the national level at Sudan Federal Ministry of Health. the data was customized and then analyzed using Epi Info7 software. Analysis was done using frequencies and percentages and the results presented in tables and figures. Permission and ethical approval were obtained from the Health Emergency and Epidemic Control Directorate at the Federal Ministry of Health.ResultsThe outbreak of mpox was confirmed after testing of initial specimens outside Sudan with positivity rate of 72%. Later the cases continued to be reported based on the clinical diagnosis and standard case definition. Out of 375 reported cases, 54.4% were males, while 45.6% were females. The age of cases ranged from one month to 78 years with majority (41.1%) of the cases were children under 5 years of age. Regarding the reported symptoms, all cases had the characteristic skin rash and 74.1% of them had fever. Other symptoms included, headache (31.5%), sore throat (30.9%) and lymphadenopathy (26.1%). For occupation, 35.7% were preschool and 10.4% were school children, 9% of cases were prisoners. Around 22 (5.8%) reported contact history with a confirmed case, while (5.6%) of the cases were imported cases. Cases were reported from 17 states with 42 affected localities (districts) with an overall attack rate of 2.36/ 100,000. The highest number of cases was reported from Gadaref (45.3%), West Darfur (25.9%), Khartoum (13.3%) and north Darfur (3.5%). In Gadaref, 146 (85.8%) of the cases were from a refugees’ camp. Started in epi week 19, the outbreak peaked in week 38 and last in week 42.ConclusionMpox was confirmed in the new Sudan for the first time with cases reported in most of states. Although importation of the virus is hypothesized, internal hidden circulation is possible and more in-depth investigation is highly recommended. The higher rate of infection among preschool, school children and refugees, highlights the need to strengthen the prevention and control measures in schools and camps. More focus on the data completeness is required for better understanding of the disease and can be ensured by the surveillance directorate through training of staff and updating of reporting forms. Strengthening the lab capacity inside the country is a necessity to ensure testing of all the clinically diagnosed cases.

594. THE IMPACT OF PATIENT CHARACTERISTICS AND NEOADJUVANT TREATMENT ON THE TUMOUR MICRO-ENVIRONMENT OF ESOPHAGEAL CANCER

Abstract Background Esophageal cancer remains associated with poor prognosis, as even with the current standards of multimodal treatment and oncologic surgery many patients show no response to treatment, or suffer early recurrence after surgery. In the current era of precision medicine, a better understanding of the tumor microenvironment (TME) is needed to identify patients with unfavourable biology, but also to illustrate the physiopathology of host reaction to treatment. The aim of this monocentric translational study was to analyse the biomolecular characteristics of esophageal cancer in relation to key clinicopathologic parameters, and in particular to the response to neoadjuvant treatment. Methods A series of patients operated for esophageal cancer with curative intent between 01.2009 and 12.2021 were included in this study. Clinicopathological data were collected, and initial biopsies and surgical specimens were reassessed by a senior GI pathologist. The immune infiltrate markers CD3, CD8, CD163, CD68, PDL1and FOXP3 were recorded as cell counts/high power field. The CPS score was used for PD-L1 quantification, whereas the Mandard regression grade (TRG) assessed pathologic response to neoadjuvant treatment (NAT). Continuous variables were compared with the Mann-Whitney-U and ANOVA tests, and categorical ones with the Chi-2 test. Significance threshold was set at p<0.05. Results Overall, 68 patients (82.4% males, mean age 62.4□9.4 years, 79.4% adenocarcinoma) were included. TME in smokers had lower M2-like (CD163+, p=0.009) and total macrophages (CD68+, p=0.001), but similar CD163/68 ratio and T-cells as non-smokers. Adenocarcinoma histology compared to squamous cell, showed higher M2-like macrophages (p=0.023), mean CPS score (p=0.038) and T-cell infiltration (p=0.006). NAT increased macrophages and cytotoxic T-cells, and decreased Treg/FoxP3 cells in the TME. Chemotherapy, compared to chemoradiation, was associated with higher T-cell TME infiltration. Good responders to NAT (TRG1-2) had similar initial TME characteristics as poor responders, but they displayed lower macrophage count upon final histology (p=0.003). Conclusions In the present series, active smoking was related to attenuated, whereas adenocarcinoma histology to enhanced M2-like macrophage infiltration of esophageal cancer TME. Neoadjuvant treatment, and especially chemotherapy, recruited macrophages and T-cells in the TME. None of the biomarkers derived from the initial biopsies were associated with response to NAT, although an increased macrophage count upon final histology was related to poor response. The present study provides valuable insight to the TME composition of esophageal cancer. However, further studies are needed to assess the exact functional role of TME elements, and specifically macrophages, and their impact on clinical outcomes.

Seismic behavior and resilience assessment of prefabricated beam–column joint with replaceable graded-yielding energy-dissipating connectors

Conventionally assembled monolithic concrete frame structures achieve structural ductility through beam-end failure, which results in structures that are difficult to repair after an earthquake. To improve the seismic and resilience performance, a prefabricated concrete beam–column joint with replaceable graded-yielding energy-dissipating connectors (RGECs) is introduced. The connectors assembled on the upper and lower sides of the beam end dissipate energy and transfer the beam-end load with the steel hinge device. By adjusting the design bearing-capacity coefficient of RGECs to precast beams, the plasticity and damage of the structure can be centered on the core energy-dissipation bending–shear components (BSCs) and buckling segment (BS) of the RGEC, and the structural function can be quickly recovered by replacing only the damaged RGECs after a seismic disaster. Moreover, compared to the conventional joints, the joint with RGEC can achieve target seismic-performance goals at different seismic-risk levels by designing BSCs and BS with graded yielding. Low-cyclic-loading tests were performed on seven full-scale beam–column joint specimens to investigate the effects of different core energy-dissipating member thicknesses, beam reinforcement ratios and loading protocols on the seismic behavior of the proposed joint. Subsequently, the damaged RGECs were replaced, and the structural-function resilience performance was evaluated in terms of the function-recovery efficiency and quality, indicated by the hysteresis response, strain development, and component energy dissipation. The experimental results proved that the beam–column joint exhibited excellent seismic performance and could realize graded-yielding energy dissipation. The damage to the specimens was concentrated in the RGECs, the key members (beams and columns) were in an elastic state, and the energy dissipation ratio of the RGEC was more than 97 %. This enables the rapid recovery of function after earthquakes. After replacing the RGEC, the hysteresis response, strain development, and component energy dissipation of the specimens were consistent with those of the initial specimens. Compared with the original specimen, the difference in each seismic index of the replaced specimen was less than 10 %. Additionally, the structural function recovered quickly, and the resilient performance was good.

Association of CSF α-Synuclein Seeding Amplification Assay Results With Clinical Features of Possible and Probable Dementia With Lewy Bodies.

The clinical diagnosis of dementia with Lewy bodies (DLB) depends on identifying significant cognitive decline accompanied by core features of parkinsonism, visual hallucinations, cognitive fluctuations, and REM sleep behavior disorder (RBD). Hyposmia is one of the several supportive features. α-Synuclein seeding amplification assays (αSyn-SAAs) may enhance diagnostic accuracy by detecting pathologic αSyn seeds in CSF. In this study, we examine how different clinical features associate with CSF αSyn-SAA positivity in a large group of clinically diagnosed participants with DLB. Cross-sectional and longitudinal CSF samples from the multicentered observational cohort study of the DLB Consortium and similar studies within the Parkinson's Disease Biomarker Program, contributed by academic medical centers in the United States, underwent αSyn-SAA testing. Participants included those clinically diagnosed with DLB and 2 control cohorts. Associations between core DLB features and olfaction with αSyn-SAA positivity were evaluated using logistic regression. CSF samples from 191 participants diagnosed with DLB (mean age 69.9 ± 6.8, 15% female), 50 age-matched and sex-matched clinical control participants, and 49 younger analytical control participants were analyzed. Seventy-two percent (137/191) of participants with DLB had positive αSyn-SAAs vs 4% of the control groups. Among participants with DLB, those who were αSyn-SAA-positive had lower Montreal Cognitive Assessment scores (18.8 ± 5.7 vs 21.2 ± 5.2, p = 0.01), had worse parkinsonism on the Movement Disorders Society Unified Parkinson's Disease Rating Scale part III (33.8 ± 15.1 vs 25.6 ± 16.4, p = 0.001), were more likely to report RBD (114/133 [86%] vs 33/53 [62%], p < 0.0001), and had worse hyposmia on the University of Pennsylvania Smell Identification Test (UPSIT) (94/105 [90%] below 15th percentile vs 14/44 [32%], p < 0.0001). UPSIT percentile had the highest area under the curve (0.87, 95% CI 0.81-0.94) in predicting αSyn-SAA positivity and participants scoring at or below the 15th percentile of age and sex normative values had 18.3 times higher odds (95% CI 7.52-44.6) of having a positive αSyn-SAA test. Among 82 participants with longitudinal CSF samples, 81 (99%) had the same αSyn-SAA result for initial and follow-up specimens. A substantial proportion of clinically diagnosed participants with DLB had negative αSyn-SAA results. Hyposmia was the strongest clinical predictor of αSyn-SAA positivity. Hyposmia and αSyn-SAA may have utility in improving the diagnostic assessment of individuals with potential DLB. This study provided Class III evidence that CSF αSyn-SAA distinguishes patients with clinically diagnosed DLB from normal controls.

Predictive analysis of breast cancer metastasis and identification of genetic markers using machine learning.

4 Background: The study devises a framework integrating machine learning (ML) paradigms with explainable artificial intelligence (XAI) to prognosticate the metastatic trajectory of breast cancer (BC) and delineate critical genomic indicators pertinent to metastasis. Methods: An examination was conducted on 98 initial BC specimens, which included 34 instances evolving into distant metastasis within a quintennial monitoring phase and 44 instances evincing no recurrence for a minimum pentad post-diagnosis. Genomic datasets underwent rigorous biostatistical scrutiny, followed by the implementation of an elastic net algorithm for feature discernment, thereby constraining the scope to a salient subset of genomic markers implicated in BC metastasis. An ensemble of advanced predictive models encompassing Light Gradient Boosting Machine (LightGBM), Categorical Boosting (CatBoost), Extreme Gradient Boosting (XGBoost), Gradient Boosting Trees (GBT), and Adaptive Boosting (AdaBoost) was deployed. Model efficacy was gauged through metrics such as accuracy, F1 score, precision, recall, the Area Under the Receiver Operating Characteristic Curve (AUC), and the Brier score. To elucidate the reasoning behind the ML predictions and to navigate the opacity inherent in such models, a SHapley Additive exPlanations (SHAP) approach was invoked. Results: The predictive acumen of the LightGBM model was superior, evidenced by a striking accuracy of 96% and an AUC of 99.3%. Parallel to biostatistical assessments, SHAP analysis leveraging XAI illuminated that augmented expression levels of specific genes, namely TSPYL5, ATP5E, CA9, NUP210, SLC37A1, ARIH1, PSMD7, UBQLN1, PRAME, and UBE2T (with statistical significance p ≤ 0.05), correlated with an escalated risk of BC metastasis. Conversely, diminished expression of CACTIN, TGFB3, SCUBE2, ARL4D, OR1F1, ALDH4A1, PHF1, and CROCC (p ≤ 0.05) was similarly associated with heightened metastatic susceptibility in BC. Conclusions: The insights garnered from this investigation may catalyze preventative strategies against BC progression and metastatic dissemination, thereby enhancing therapeutic efficacy through personalized intervention modalities for BC patients.

The taxonomic composition and chronology of a museum collection of Coleoptera revealed through large-scale digitisation

IntroductionHistoric museum collections hold a wealth of biodiversity data that are essential to our understanding of the rapidly changing natural world. Novel curatorial practices are needed to extract and digitise these data, especially for the innumerable pinned insects whose collecting information is held on small labels.MethodsWe piloted semi-automated specimen imaging and digitisation of specimen labels for a collection of ~29,000 pinned insects of ground beetles (Carabidae: Lebiinae) held at the Natural History Museum, London. Raw transcription data were curated against literature sources and non-digital collection records. The primary data were subjected to statistical analyses to infer trends in collection activities and descriptive taxonomy over the past two centuries.ResultsThis work produced research-ready digitised records for 2,546 species (40% of known species of Lebiinae). Label information was available on geography in 91% of identified specimens, and the time of collection in 39.8% of specimens and could be approximated for nearly all specimens. Label data revealed the great age of this collection (average age 91.4 years) and the peak period of specimen acquisition between 1880 and 1930, with little differences among continents. Specimen acquisition declined greatly after about 1950. Early detected species generally were present in numerous specimens but were missing records from recent decades, while more recently acquired species (after 1950) were represented mostly by singleton specimens only. The slowing collection growth was mirrored by the decreasing rate of species description, which was affected by huge time lags of several decades to formal description after the initial specimen acquisition.DiscussionHistoric label information provides a unique resource for assessing the state of biodiversity backwards to pre-industrial times. Many species held in historical collections especially from tropical super-diverse areas may not be discovered ever again, and if they do, their recognition requires access to digital resources and more complete levels of species description. A final challenge is to link the historical specimens to contemporary collections that are mostly conducted with mechanical trapping of specimens and DNA-based species recognition.

Grade Heterogeneity in High-Grade Urothelial Carcinomas: Does It Have an Impact on the Survival of Patients With Intermediate/High-Risk Nonmuscle-Invasive Bladder Cancer Who Received Adequate Adjuvant Bacillus Calmette-Guérin Therapy?

We aimed to compare recurrence-free survival (RFS) and progression-free survival (PFS) of the patients with pure high-grade (HG) vs mixed-grade (MG) nonmuscle-invasive bladder cancer who received adequate bacillus Calmette-Guérin therapy. We conducted a retrospective cohort analysis using data from an institutional database. The study included patients diagnosed with HG nonmuscle-invasive bladder cancer at the initial transurethral resection specimen between 2010 and 2020. The initial transurethral resection specimens of all patients were reevaluated by a dedicated uropathologist. The percentage of low-grade tumor areas accompanying HG areas was determined for each case. Time-to-event analysis was performed using the Kaplan-Meier method. RFS and PFS rates were compared between groups. Of the 203 patients enrolled in the study, 69 (34%) had MG tumors. Recurrence was observed in 41 out of 134 patients (30.6%) in the HG group and in 19 out of 69 patients (27.5%) in the MG group. The 36-month RFS rates were 69% (CI: 62-77) and 72% (CI: 62-83) for the HG-urothelial carcinoma (UC) and MG-UC groups, respectively. The RFS rates were similar between groups (log-rank, P = .58). Progression was observed in 22 out of 134 patients (16.4%) in the HG group and in 4 out of 69 patients (5.8%) in the MG group. The 36-month PFS rates were 84% (CI: 77-90) and 94% (CI: 89-100) for the HG-UC and MG-UC groups, respectively. The pure HG-UC group had a worse PFS than the MG-UC group (log-rank, P = .042). Multivariate analysis demonstrated that age and tumor grade were significant risk factors for the development of progression. The indication of MG-UC category separately from pure HG carcinomas in the pathology report seems to be an important issue that can guide patient management. In this way, both more accurate risk classification and more accurate patient counseling can be performed. More importantly, the treatment plan can be made more accurately. For more precise conclusions, our results should be supported by prospective studies with larger sample size.

A quantitative description of the influence of plastic dissipation on crack growth behaviors

This paper has transferred the influence of plastic dissipation on the crack driving force into the crack growth resistance curve based on a displacement quantity defined at the current crack tip. Such a displacement is the crack-tip-opening displacement of the corresponding stationary crack for an elastic–plastic growing crack and represents the plastic wake height. Then, this displacement-based resistance curve provides a quantitative description of the plastic deformation influences during crack growth. This paper has three novel points: 1) the crack-tip-opening displacement for an imaginary stationary crack is divided into the separation displacement and the plastic wake height, in which the separation displacement is related to the crack driving force and the plastic wake height is correlated with the plastic influence term. 2) A unified constraint of the traction-separation law (TSL) for the cohesive zone is provided by the relation between separation displacement and the crack driving force, which can shed further light on how to choose a proper TSL. 3) According to the relation between the plastic wake height and the plastic dissipation term, the influence of plastic deformation on the crack driving force is found to be independent of initial crack length, specimen width and geometrical type as long as the crack tip plastic zone does not reach the outer boundary or merge with the plastic zone of the outer boundary.

Detection of molecular residual disease in stage II and III melanoma utilizing circulating tumor DNA.

e21564 Background: Overall survival for patients with melanoma has significantly improved with advancements in immunotherapy, especially with immune checkpoint inhibitors and BRAF/MEK inhibitors becoming standard of care for advanced melanoma. However, the decision to proceed with adjuvant therapy should be considered against the risk of adverse side effects, particularly in early-stage melanoma patients. Accurate biomarkers are needed to risk stratify patients, determine who will most likely benefit from adjuvant therapy, and identify when the ideal time is to initiate treatment. This study evaluates the prognostic value of personalized, tumor-informed circulating tumor DNA (ctDNA) testing in patients with stage II and III melanoma. Methods: In this real-world study, plasma samples (n =429) were analyzed from 90 stage IIA-IIID cutaneous melanoma patients treated at Rush University Medical Center between 03/30/2021 and 01/30/2024. A clinically-validated, personalized, tumor-informed 16-plex PCR assay (SignateraTM, Natera, Inc.) was used for detection and quantification of ctDNA in plasma samples. Results: Personalized, tumor-informed ctDNA assays were created using tissue samples from either initial biopsy or surgical excision specimen. Assay design was successful for 100% (90/90) of patients with sufficient tissue; test requests for 4 patients could not proceed due to insufficient tissue. ctDNA was detectable in 28% (25/90) of patients at one or more time points. There was a higher ctDNA-positivity rate in stage III patients (20/50, 40%) compared to stage II patients (5/40, 13%). Of the 25 patients with identifiable ctDNA during surveillance, 13 tested positive on the initial test (2 stage II and 11 stage III). Eighteen of the 25 ctDNA-positive patients received immunotherapy; eight patients achieved sustained ctDNA clearance, 2 had transient clearance, 2 have remained positive on ctDNA testing, and 6 continue to receive adjuvant IO and follow-up ctDNA testing. Clinical or radiographic recurrence occurred in 11/90 patients, 10 of whom tested positive for ctDNA. Conclusions: Personalized, tumor-informed ctDNA offers an adjunct to conventional monitoring for melanoma patients to detect molecular residual disease and was found to be prognostic in our patient cohort. Prospective studies are needed to evaluate the role of ctDNA in clinical decision making for surveillance imaging intervals and appropriate initiation, intensification, or discontinuation of adjuvant therapy.

Unveiling the self-annealing phenomena and its effect on microstructure and texture evolution in the room temperature rolled Cu-0.13Sn-0.04Mg alloy

ABSTRACT In this study, we investigated the microstructural evolution of a Cu-0.13Sn-0.04Mg alloy that underwent heat treatment followed by room temperature rolling (RTR). Initially heat-treated specimens were rolled at room temperature (RT) with reduction ratios (RR) of 40% and 75% to perform microstructural and crystallographic textural analyses. Electron backscattered diffraction (EBSD) and transmission electron microscopy (TEM) were utilise to examine both initial and deformed microstructures. Both exhibited heterogeneous microstructural distributions. Shear bands (SBs) existed in the initial specimen and became main sites for the nucleation of new grains during heat treatment. A denser presence of SBs was noted in the RTR specimens. Remarkably, an unusual self-annealing phenomenon was observed in these specimens, culminating in the emergence of recrystallized grains at RT. A plethora of such grains was observed in the severely deformed specimens, with numerous nucleating grains appearing proximal to the SBs or deformed grain boundaries (GBs). Time dependent microstructure evolution was observed via ex-situ EBSD technique in the compressed specimens. Formation of new grains, increase in high angle grain boundaries (HAGBs), and dislocation annihilations were observed with the progress of time. The crystallographic texture evolution in the initial specimen was predominantly influenced by the S component. At lower strains, the fractions of Copper component increased, whereas at higher strains, a greater fraction of Brass and S components were induced. Following a 40% RR, a saturation in hardness value was observed, which could be potentially attributable to an accelerated rate of RT recrystallization in the case of 75% RR.

Experimental investigation of the polymer-metal hybrids interfacial bonding fabricated by fused deposition modeling

In this paper, the fabrication of polymer-metal hybrids by fused deposition modeling was evaluated. 6061 aluminum alloy and polylactic acid were used in the manufacturing process. Also, to strengthen the bonding between the metal and polymer components, a two-component epoxy adhesive was used. The pull-off adhesion test was performed to evaluate the interfacial bonding strength of the specimens. In this study, the effect of bed temperature, print speed, printer nozzle diameter, and aluminum sheet surface roughness on the bond strength of polymer-metal hybrids has been investigated. The results showed that increasing the bed temperature, and aluminum sheet surface roughness, and also decreasing the print speed led to increase the bond strength of polymer-metal hybrids. Finally, by using the experimental data, an optimal specimen was produced. The interfacial bonding strength of the optimal specimen is about 64% stronger than the initial specimen.

Follow-up of women with cervical adenocarcinoma in situ treated by conization: A single centre clinical experience

ObjectiveHysterectomy has been the historical gold standard final step in the treatment algorithm of adenocarcinoma in situ (AIS) recommended by most North American colposcopy guidelines. AIS disproportionately affects young childbearing age women, therefore a fertility sparing treatment option is desirable. Our study examines the impact of conservative treatment of AIS with conization followed by serial surveillance. MethodsA retrospective chart review was completed of patients treated for AIS from 2006 to 2020. Charts were identified by pathologic diagnosis of AIS on cervical and uterine specimens. Charts were excluded if AIS was not treated with conization, if AIS was not confirmed on initial conization specimen, or if invasive disease was found at initial conization. Results121 patient charts were analyzed. Median age of patients at first conization and hysterectomy was 34.8 and 40.9, respectively. First conization was by Cold Knife Cone in 58% of patients, and by Loop Electrosurgical Excisional Procedure in 42% of patients. Median follow-up period in our study was 609 days. 5% of patients had recurrence, with only one patient who recurred as cancer. One case of recurrence had a positive initial conization margin. Median time to recurrence was 700 days. 47% of patients underwent eventual hysterectomy. Residual AIS was found in 23% of hysterectomy specimens. Adenocarcinoma was diagnosed on hysterectomy specimen in four patients. ConclusionOur study demonstrates the oncologic safety of treating AIS with conization and serial surveillance. Routine hysterectomy completed as a part of the AIS treatment algorithm, as in current clinical guidelines, is unnecessary.

Predicting fatigue crack growth rate of cement-based and asphalt paving materials based on indirect tensile cyclic loading tests

Fatigue crack growth rate (FCGR) is a critical indicator that reflects the rate at which material deterioration occurs under cyclic loads. However, there is currently a lack of a mechanistic quantitative analysis and prediction of the FCGR of paving materials under external indirect tensile (IDT) cyclic loads. To address this issue, this study aims to develop a mechanistic model for quantitative analysis and prediction of the FCGR in paving materials subjected to external IDT cyclic loads based on the J-integral based Paris’ law. Two types of paving materials, namely cement-treated aggregates and asphalt mixtures, were selected to demonstrate the results and model of the FCGR. The results indicate that the derived J-integral serves as the driving force for crack growth and is influenced by horizontal tensile stress, initial resilient modulus, damage density, specimen size, and surface energy of the paving materials. The fatigue life of cement-treated aggregates is primarily influenced by the crack initiation stage, while for asphalt mixtures, the crack growth stage plays a more significant role. The application of Paris’ law is found to be effective in predicting the FCGR at stable crack growth stage. The coefficients of Paris’ law exhibit minimal variation across different stress levels and loading frequencies, and can be utilized to evaluate the fatigue crack resistance of different paving materials.