High Degree Of Concordance Research Articles

Optimizing anemia management using artificial intelligence for patients undergoing hemodialysis

Patients with end-stage kidney disease (ESKD) frequently experience anemia, and maintaining hemoglobin (Hb) levels within a targeted range using erythropoiesis-stimulating agents (ESAs) is challenging. This study introduces a gated recurrent unit-attention-based module (GAM) for efficient anemia management among patients undergoing chronic dialysis and proposes a novel alert system for anticipating the need for red blood cell transfusions. Data on demographic characteristics, dialysis metrics, drug administration, laboratory tests, and transfusion history were retrospectively collected from patients undergoing hemodialysis at Kangwon National University Hospital between 2017 and 2022. After preprocessing, a final dataset of 252 patients was used for model training. Our model functions in two major phases: (1) Hb level prediction and ESA dose recommendation and (2) transfusion alert framework. The GAM model outperformed traditional machine learning algorithms, including linear regression, XGBoost, and multilayer perceptron, in predicting Hb levels (R-squared value = 0.60). The model also demonstrated a recommendation accuracy of 0.78 compared to that of clinical experts, indicating a high degree of concordance with the ESA dosing recommendations. Additionally, the model exhibited considerably high accuracy (0.99) for transfusion alarms. Thus, the GAM model holds promise for improving anemia management in patients with ESKD by optimizing ESA dosages and providing timely transfusion alerts.

Direct oral anticoagulant approvals by four major regulatory agencies: a cross-sectional analysis of premarket and postmarket evidence

ObjectivesTo compare the premarket and postmarket evidence of safety and efficacy of direct oral anticoagulants approved for stroke prevention in atrial fibrillation patients across four major regulatory agencies.DesignCross-sectional.SettingEuropean Medicines Association...

Systematic review and feasibility study on pre-analytical factors and genomic analyses on archival formalin-fixed paraffin-embedded breast cancer tissue

Formalin-fixed paraffin-embedded (FFPE) tissue represents a valuable source for translational cancer research. However, the widespread application of various downstream methods remains challenging. Here, we aimed to assess the feasibility of a genomic and gene expression analysis workflow using FFPE breast cancer (BC) tissue. We conducted a systematic literature review for the assessment of concordance between FFPE and fresh-frozen matched tissue samples derived from patients with BC for DNA and RNA downstream applications. The analytical performance of three different nucleic acid extraction kits on FFPE BC clinical samples was compared. We also applied a newly developed targeted DNA Next-Generation Sequencing (NGS) 370-gene panel and the nCounter BC360® platform on simultaneously extracted DNA and RNA, respectively, using FFPE tissue from a phase II clinical trial. Of the 3701 initial search results, 40 articles were included in the systematic review. High degree of concordance was observed in various downstream application platforms. Moreover, the performance of simultaneous DNA/RNA extraction kit was demonstrated with targeted DNA NGS and gene expression profiling. Exclusion of variants below 5% variant allele frequency was essential to overcome FFPE-induced artefacts. Targeted genomic analyses were feasible in simultaneously extracted DNA/RNA from FFPE material, providing insights for their implementation in clinical trials/cohorts.

Design of a microstrip Wilkinson power divider using a low pass filter with the particle swarm optimization algorithm

In this paper, a microstrip Wilkinson power divider (MWPD) based on particle swarm optimization (PSO) algorithm is designed, simulated, and fabricated using novel resonators. In addition, attenuators and open-ended stubs are incorporated to generate a broad cut-off band and reduce unwanted harmonics. The proposed power divider has a central frequency of 1 GHz. The performance of each used resonator is analyzed based on lumped-element circuit models.The L and C parameters of the equivalent circuit of the used resonators are predicted and optimized with the assistance of the PSO method. The subsequent phase was the fabrication of the proposed MWPD, after which its performance was evaluated in the light of the results obtained from the simulation. It was discovered that there was a high degree of concordance between the two. On the other hand, the fabricated circuit has several benefits, including a suitable S12 of − 3.15 dB, a high return loss of less than − 24 dB at the operating frequency, a compact size of 0.058 λg\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${\\varvec{\\lambda}}_{{\\varvec{g}}}$$\\end{document} × 0.064 λg\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${\\varvec{\\lambda}}_{{\\varvec{g}}}$$\\end{document}, and the ability to remove undesired harmonics. The results show a high level of suppression of the unwanted harmonics (up to the 16th harmonic) and a great responsiveness in the passband, while having very low ripple. As a result, the proposed circuit may be used in a wide variety of electronic devices, such as radar transmitter and receiver circuits, and many other high-frequency systems.

A New Method for the Follow-Up of Patients with Alopecia Areata.

Background: Teledermatology is the application of information and telecommunication technologies in the field of dermatology to provide remote care services based on the exchange of clinical information within a network of professionals or between professionals and patients. Tele-trichoscopy is a non-invasive, inexpensive, and easy-to-use method that applies the principle of surface microscopy at different magnifications. Alopecia areata is a non-scarring alopecia with a chronic evolution, which often needs a close follow-up. Objectives: The aim of our work was to analyze the possible benefits of telemedicine for the follow-up of patients with alopecia areata. Materials and Methods: We enrolled patients with alopecia areata, identified during the first trichological evaluation, and we divided the patients into two groups. One group was provided with the devices necessary for a telemedicine follow-up. The other group had a conventional follow-up. The total follow-up time was one year. All of the patients' photos were blindly evaluated by a team of expert dermatologists who were asked to indicate the quality of the images. The photos were also evaluated to identify disease markers. During the follow-up period, questionnaires were administered to both groups of patients to assess the quality of the visit, the level of patient satisfaction, and to identify any issues encountered by the patients. Results: There was a high degree of concordance between the images obtained by outpatient trichoscopy and those obtained by telemedicine. The satisfaction levels were the same between the patients followed via telemedicine and those seen in the outpatient clinic. Conclusions: Telemedicine applied to trichology using trichoscopy was proven to be a valid system for managing the follow-up of patients suffering from chronic recurrent scalp diseases and, above all, for maintaining continuity of care.

Optimization of the VARTM Process for Prototyping a Bumper Using Hybrid Composite Materials

To provide an alternative for manufacturing auto parts using composite materials, the Vacuum Assisted Resin Transfer Molding (VARTM) process was utilized to prototype the bumper for the Chevrolet Aveo vehicle. This technique emerges as an alternative for composite material manufacturing, allowing for rapid and high-quality production of advanced composites. In this study, a hybrid composite material reinforced with fiberglass, cabuya fiber, IN2 epoxy resin, an infusion mesh, peel ply, and a vacuum bag was employed. To optimize the VARTM process in bumper prototyping, several simulations of resin flow were conducted with different locations of resin injection and vacuum entry points. Autodesk Moldflow Insight software facilitated the modification and addition of resin injection points to observe the flow evolution, thus determining the filling time for each proposed design. Six different designs were applied for the bumper mold filling. The proposed linear flow design reduced the total filling time of the bumper mold by 81.56% compared to the other five designs analyzed. The result of the numerical simulation was validated through the experimental process, where a high degree of concordance in the mold filling time was achieved between both methods.

Targeted Screening of Curcumin Derivatives as Pancreatic Lipase Inhibitors Using Computer-Aided Drug Design.

Curcumin has demonstrated promising preclinical antiobesity effects, but its low bioavailability makes it difficult to exert its full effect at a suitable dose. The objective of this study was to screen curcumin derivatives with enhanced bioavailability and lipid-lowering activity under the guidance of computer-aided drug design (CADD). CAAD was used to perform virtual assays on curcumin derivatives to assess their pharmacokinetic properties and effects on pancreatic lipase activity. Subsequently, 19 curcumin derivatives containing 5 skeletons were synthesized to confirm the above virtual assay. The in vitro pancreatic lipase inhibition assay was employed to determine the half-maximal inhibitory concentration (IC50) of these 19 curcumin derivatives. Based on CADD analysis and in vitro pancreatic lipase inhibition, 2 curcumin derivatives outperformed curcumin in both aspects. Microscale thermophoresis (MST) experiments were employed to assess the binding equilibrium constants (K d) of the aforementioned 2 curcumin derivatives, curcumin, and the positive control drug with pancreatic lipase. Through virtual screening utilizing a chemoinformatics database and molecular docking, 6 derivatives of curcumin demonstrated superior solubility, absorption, and pancreatic lipase inhibitory activity compared to curcumin. The IC50 value for 1,7-bis(4-hydroxyphenyl)heptane-3,5-dione (C4), which displayed the most effective inhibitory effect, was 42.83 μM, while the IC50 value for 1,7-bis(4-hydroxy-3-methoxyphenyl)heptane-3,5-dione (C6) was 98.62 μM. On the other hand, the IC50 value for curcumin was 142.24 μM. The MST experiment results indicated that the K d values of C4, C6, and curcumin were 2.91, 18.20, and 23.53 μM, respectively. The results of the activity assays exhibited a relatively high degree of concordance with the outcomes yielded by CADD screening. Under the guidance of CADD, the targeted screening of curcumin derivatives with excellent properties in this study exhibited high-efficiency and low-cost benefits.

Does the prevalence of depression in patients with malignancies vary with the diagnostic approach: A study comparing the four diagnostic approaches.

Very few studies have compared different diagnostic approaches to diagnose depression in patients with cancers. To compare the different diagnostic approaches used for diagnosing depression in patients with cancers. This cross-sectional study included 200 patients (diagnosed with cancer at least 3 months prior to recruitment) attending the outpatient services who were assessed on diagnostic and statistical manual, fifth edition (DSM-5) criteria for depression. Additionally, these patients were also assessed using the inclusive, exclusive, and substitutive criteria for depression using a semistructured interview. Patients completed Patient Health Questionnaire-9 (PHQ-9). The mean age of the patients was 50.28 years (S.D. M14.11). Females outnumbered males. The mean age of onset of malignancy was 47 years (S.D 14.03), and the mean time since diagnosis of cancer was 35.45 years (S.D 36.87). The prevalence of depression was the highest (38.5%) when estimated using the PHQ-9 and was the lowest (21.5%) when assessed using exclusive criteria for depression. All approaches had high degree of concordance with the DSM-5 criteria for depression. A significant proportion of patients with cancer suffer from depression, and the prevalence is influenced by the diagnostic method.

Can seasonal prediction models capture the Arctic mid‐latitude teleconnection on monthly time scales?

AbstractThis study explores Arctic warming's effect on Eurasia's temperature variability, notably the warm Arctic–cold Eurasia (WACE) pattern, and assesses seasonal prediction models' accuracy in capturing this phenomenon and its monthly variation. Arctic warming events are categorized into deep Arctic warming (DAW), shallow Arctic warming (SAW), warming aloft (WA), and no Arctic warming (NOAW), based on the temperatures at 2 m and 500 hPa in the Barents–Kara Sea. It is revealed that DAW events are significantly correlated with monthly cold temperature anomalies in East Asia, predominantly occurring in January–February, excluding December. This study evaluates two primary capabilities of seasonal prediction models: their proficiency in forecasting these Arctic warming events, particularly DAW, and their ability to replicate the spatial patterns associated with DAW. Some models demonstrated notable predictive skill for DAW events, with enhanced performance in January and February. Regarding spatial pattern reproduction, models showed limited alignment with the reference dataset over the Northern Hemisphere (above 25° N) in December, whereas a higher degree of concordance was observed in January–February. This indicates their capability in capturing the atmospheric circulation patterns associated with DAW, pointing to areas where model performance can be enhanced.

Concordance factors in craniosynostosis twins: a meta-analysis and case report

Introductions: Craniosynostosis is a condition where the cranial sutures close prematurely. It is influenced by both genetics and environment. This paper focuses on craniosynostosis in twins, which is an understudied area. It presents a case report of male identical twins and conducts a meta-analysis based on 34 articles to understand the factors affecting concordance in twins who have craniosynostosis. The study considers factors such as zygosity, gender, genetic syndromes, and the type of synostosis. Material and methods: A meta-analysis was conducted on 105 twin pairs (210 patients) identified from studies carried out between 1963 to 2023. The eligible studies, based on PICO criteria, included case reports and case series focusing on twins with craniosynostosis. A systematic literature search was conducted on PUBMED and Mendeley platforms to gather data on gestational age, zygosity, genetic syndromes, affected sutures, and concordance. Results: The report is about two identical twin brothers who had sagittal and metopic suture synostosis. They were treated successfully with cranial remodeling surgery. In a meta-analysis of 105 twin pairs (210 patients) , a total of 25.9% showed concordance. The study found a significant difference in concordance between monozygotic (45.3%) and dizygotic (7.3%) twins. The analysis also revealed that twins with scaphocephaly had a higher degree of concordance than those with trigonocephaly (46.7% vs. 18.9%, respectively). The study did not find any significant correlation between gender, the presence of genetic syndromes, and concordance. Conclusion: This investigation highlights the complex interplay of genetic and environmental factors in craniosynostosis in twins. The higher concordance in monozygotic twins emphasizes the genetic basis. These findings validate existing literature and provide new insights.

Concurrent Validity of PROMIS and LD-SRS Scores in Pediatric Patients With Lower Limb Differences.

We sought to assess the concurrent validity of select Patient Reported Outcomes Measurement Information System (PROMIS) domains and Limb Deformity-Scoliosis Research Society (LD-SRS) scores. We prospectively administered PROMIS - 25 (including anxiety, depression, fatigue, pain interference, peer relationships, and physical function) and LD-SRS questionnaires to 46 consecutive pediatric patients with lower limb differences, presenting to a single surgeon for reconstruction. Concurrent validity between various subdomains of the 2 outcome measures was assessed through Pearson's correlation, with significance defined as P <0.05. The strength of correlation was interpreted by Evans criteria: absolute r value <0.20 indicating very weak correlation; 0.20 to 0.39, weak; 0.40 to 0.59, moderate; 0.60 to 0.79, strong; and 0.8 or greater indicating very strong correlation. The LD-SRS Pain, Function, and Mental Health domains most strongly correlated with the PROMIS pain interference ( r =-0.79, P <0.001), physical function ( r =0.74, P <0.001), and anxiety ( r =-0.68, P <0.001) domains, respectively. In addition, LD-SRS pain strongly correlated with PROMIS physical function ( r =0.61, P <0.001) and LD-SRS function with PROMIS pain interference ( r =-0.72, P <0.001). All PROMIS domains significantly correlated with total LD-SRS scores. PROMIS pain interference ( r =-0.79, P <0.001), physical function ( r =0.67, P <0.001), and fatigue ( r =-0.60, P <0.001) domains demonstrated the strongest correlations with the total LD-SRS score. The significant concurrent validity between LD-SRS and multiple PROMIS domains suggests considerable overlap, and perhaps redundancy, between these 2 outcome measures. Given the high degree of concordance and the advantage of computer adaptive testing (CAT) in mitigating administrative burden and survey fatigue, along with the ability to compare outcomes across a wider group of children with a variety of underlying diagnoses, select PROMIS domains may be a viable alternative to LD-SRS score for assessing patient-reported outcomes when treating pediatric patients with lower limb deformities. A larger, multi-center study including pediatric patients with lower limb differences from a diverse background, including age, etiology, native language, and ethnicity, would be helpful to externally validate our findings. Level-I.

Application of narrow band imaging in the diagnosis of pharyngeal tumors

BackgroundNarrow-band imaging (NBI) endoscopy is used in various tumor detection and is important in detecting early tumors. ObjectiveTo explore the application value of NBI endoscopy in diagnosing pharyngeal tumors. Material and methodsNinety-one patients with pharyngeal masses who attended the Department of Otorhinolaryngology, Head and Neck Surgery in Gansu Provincial Hospital from January 2023 to February 2024 were selected, and NBI and white light (WL) endoscopy were applied to examine the pharynx and the relationship between the two was observed. SPSS 25.0 software was used for statistical analysis. ResultsThe sensitivity of NBI endoscopy for diagnosing laryngeal malignant lesions was 92.0 %, the specificity was 93.0 %, the positive predictive value was 88.5 %, and the negative predictive value was 95.2 %, with a high degree of concordance between the results of NBI endoscopy and the pathology; WL endoscopy had a sensitivity of 64.0 %, a specificity of 76. 7 %, a positive predictive value of 61.5 %, and a negative predictive value of 78.6 %, with WL endoscopic findings had moderate concordance with pathology. The diagnostic accuracy of NBI endoscopy was higher than that of WL endoscopy for both benign and malignant lesions and precancerous lesions. ConclusionNBI endoscopy can detect laryngeal cancer lesions more accurately.

On the Concordance of Romantic and Sexual Feelings and Identity Among University Students in Taiwan.

The degree to which romantic and sexual feelings correspond to one's sexual identity may signify how a person comes to embrace a specific sexual identity. People who endorse an essentialist perspective may expect to see a high degree of concordance between feelings and identity, and a lack of concordance may be associated with negative consequences. People who endorse a social constructionist perspective may view sexual identity as constructed in situ; a lack of concordance is inevitable and may not be associated with negative consequences. This research tests the levels of concordance of feelings and identity by comparing those with and without romantic and sexual feelings using risk ratios and odds ratios. A representative sample of college students in Taiwan was recruited (N = 3882, with 2440 females and 2988 who identified as heterosexual). The findings suggest that (1) people's romantic and sexual feelings largely correspond to their sexual identity, with all risk ratios and odds ratios higher than 1; (2) the concordance was at its lowest level among those with different-sex feelings; (3) gender differences in concordance were trivial; (4) individuals who were questioning their identity were the least clear about what they expect and want in intimate relationships; and (5) no general negative consequences in intimate relationships were observed among discordant/branched individuals. Implications regarding romantic and sexual feelings, sexual identity, and intimate relationships are further discussed.

Analysis of factors influencing pancreatic fistula after minimally invasive pancreaticoduodenectomy and establishment of a new prediction model for clinically relevant pancreatic fistula

BackgroundPostoperative pancreatic fistula (POPF) is the most prevalent complications following minimally invasive pancreaticoduodenectomy (MIPD). Only one model related to MIPD exists, and previous POPF scoring prediction methods are based on open pancreaticoduodenectomy patients. Our objectives are to determine the variables that may increase the probability of pancreatic fistula following MIPD and to develop and validate a POPF predictive risk model.MethodsData from 432 patients who underwent MIPD between July 2015 and May 2022 were retrospectively collected. A nomogram prediction model was created using multivariate logistic regression analysis to evaluate independent factors for POPF in patients undergoing MIPD in the modeling cohort. The area under the curve (AUC) of the receiver operating characteristic curve (ROC) and the calibration curve were used to verify the nomogram prediction model internally and externally within the modeling cohort and the verification cohort.ResultsMultivariate logistic regression analysis showed that body mass index (BMI), albumin, triglycerides, pancreatic duct diameter, pathological diagnosis and intraoperative bleeding were independent variables for POPF. On the basis of this information, a model for the prediction of risks associated with POPF was developed. In accordance with the ROC analysis, the modeling cohort's AUC was 0.819 (95% CI 0.747–0.891), the internal validation cohort's AUC was 0.830 (95% CI 0.747–0.912), and the external validation cohort's AUC was 0.793 (95% CI 0.671–0.915). Based on the calibration curve, the estimated values of POPF have a high degree of concordance with the actual values that were measured.ConclusionsThis model for predicting the probability of pancreatic fistula following MIPD has strong predictive capacity and can provide a trustworthy predictive method for the early screening of high-risk patients with pancreatic fistula after MIPD and timely clinical intervention.

Performance evaluation and parameter estimation of the advanced primary filtration (APF) process in wastewater treatment plants

Conventional technologies employed in wastewater treatment plants (WWTPs) demand significant energy consumption. Concurrently, the wastewater infrastructure is experiencing a heavy strain as a result of the increased influent loads and pollutants. Advanced primary filtration (APF) is an emerging wastewater treatment process for early removal of suspended solids from raw wastewater. In this work, the APF process comprises of a two-stage filtration system, consisting of a proprietary rotating belt filter (RBF) (collectively known as microsieve) followed by a proprietary continuous backwash upflow media filter (CBUMF). The principal focus of this study is the assessment of the APF process performance, and the prediction of the total suspended solids (TSS) effluent concentrations of the APF process, using a parameter estimation method. According to pilot scale experimental results, the percentages of TSS (average TSS removal rate of 51 %) and biological oxygen demand (BOD5) (average BOD5 removal rate of 30 %), removed by the microsieve were notably higher compared to conventional primary treatment (sedimentation). The removal efficiency of the APF process during stable operation, varied from 69 to 86 % for TSS, as compared to 50–70 % typically achieved with primary sedimentation. The removal performance of BOD5 varied from 44 to 82 %, as compared to 25 to 40 % typically achieved with primary sedimentation. The chemical oxygen demand (COD) removal rates for the APF process ranged between 62 and 90%, as compared to 25–40 % typically achieved with primary sedimentation. The early removal of TSS prior to aeration tank has the potential to significantly enhance the capacity of the WWTP and decrease the energy requirements of the aeration tank. A high degree of concordance between model predictions and experimental data was observed. This study demonstrated the potential of using the APF process for the early removal of TSS from raw municipal wastewater just upstream of the aeration tank.

Concordance between cytological and histopathological grading in invasive breast carcinoma – A cross sectional study

Invasive Breast carcinoma means that the cancer has spread beyond the ducts/lobules into the surrounding tissue. The present 2 year study was carried out at a tertiary care hospital to find the concordance between cytological and histopathological grading in invasive breast carcinoma. It included all the 100 cases of invasive breast carcinoma diagnosed on histopathology during this period with available cytology reports. Concordance of Robinson's cytological grading system was calculated in each grade with respect to histological grading. All cases evaluated for presence of metastasis to axillary lymph nodes. We found Concordance rate between cytological and histological grade as 76%. The coefficient of correlation between cytological grade and histological grade was 0.83 and P value was &amp;#60;0.001 which indicated a strong correlation and significant association between the cytological and histological grade. High degree of concordance is seen between cytological and histopathological grading system. Preoperative grading using FNAC helps in determining neo adjuvant chemotherapy as well as prognosis. This grading should be included in cytology reports on a regular basis because it correlates well with histological grade.

Moving towards on-site detection of Shiga toxin-producing Escherichia coli in ready-to-eat leafy greens

Rapid identification of Shiga toxin-producing Escherichia coli, or STEC, is of utmost importance to assure the innocuousness of the foodstuffs. STEC have been implicated in outbreaks associated with different types of foods however, among them, ready-to-eat (RTE) vegetables are particularly problematic as they are consumed raw, and are rich in compounds that inhibit DNA-based detection methods such as qPCR. In the present study a novel method based on Loop-mediated isothermal amplification (LAMP) to overcome the limitations associated with current molecular methods for the detection of STEC in RTE vegetables targeting stx1 and stx2 genes. In this sense, LAMP demonstrated to be more robust against inhibitory substances in food. In this study, a comprehensive enrichment protocol was combined with four inexpensive DNA extraction protocols. The one based on silica purification enhanced the performance of the method, therefore it was selected for its implementation in the final method. Additionally, three different detection chemistries were compared, namely real-time fluorescence detection, and two end-point colorimetric strategies, one based on the addition of SYBR Green, and the other based on a commercial colorimetric master mix. After optimization, all three chemistries demonstrated suitable for the detection of STEC in spiked RTE salad samples, as it was possible to reach a LOD50 of 0.9, 1.4, and 7.0 CFU/25 g for the real-time, SYBR and CC LAMP assays respectively. All the performance parameters reached values higher than 90 %, when compared to a reference method based on multiplex qPCR. More specifically, the analytical sensitivity was 100, 90.0 and 100 % for real-time, SYBR and CC LAMP respectively, the specificity 100 % for all three assays, and accuracy 100, 96 and 100 %. Finally, a high degree of concordance was also obtained (1, 0.92 and 1 respectively). Considering the current technological advances, the method reported, using any of the three detection strategies, demonstrated suitable for their implementation in decentralized settings, with low equipment resources.

Exploring HCl-HCl interactions: QZVPP calculations, improved Lennard-Jones potential, and second virial coefficient analysis for thermodynamics and industrial applications.

In this paper, we present a comprehensive analysis of HCl-HCl interactions, including QZVPP calculations, energy fitting, conformation validation, and the determination of the second virial coefficient B using improved Lennard-Jones (ILJ) potential parameters. To acquire accurate interaction energies, initial QZVPP calculations are performed on approximately 1851 randomly generated HCl-HCl conformations. Then, these energies are used to fit an improved Lennard-Jones potential energy surface, allowing for a robust description of HCl-HCl interactions. The ILJ potential parameters are then used to validate particular HCl dimer conformations, ensuring their stability and consistency with experimental observations. The correlation between calculated and experimental conformations strengthens the validity of the ILJ potential parameters. In addition, the second viral coefficient B is calculated at various temperatures using the ILJ potential. The obtained B values are compared to experimental data, demonstrating close agreement, and validating the ILJ potential's ability to accurately capture the intermolecular interactions and gas-phase behavior of the HCl-HCl system. The results of this study demonstrate the effective implementation of QZVPP calculations, energy fitting, and ILJ potential parameters in validating HCl-HCl conformations and accurately determining the second virial coefficient B. The high degree of concordance between calculated B values and experimental data demonstrates the validity of the ILJ potential and its suitability for modeling HCl-HCl interactions. This research contributes to a greater comprehension of HCl-HCl interactions and their implications for numerous chemical and atmospheric processes. The validated conformations, energy fitting method, and calculated second virial coefficients provide valuable instruments for future research and pave the way for more accurate modeling and simulations of HCl-HCl systems.

Expression Patterns of ER, PR, HER-2/neu and p53 in Association with Nottingham Tumour Grade in Breast Cancer Patients

Objectives: Recent molecular studies show that breast cancer (BC) is a heterogeneous disease, and several molecular changes may accumulate over time to influence treatment response. As a result, employing reliable molecular biomarkers to monitor these modifications may help deliver personalised treatment. However, this may be unrealistic in the resource-limited parts of the world. Thus, this study aimed to investigate the expression pattern of hormone receptors and p53 tumour suppressor using immunohistochemistry (IHC) in BC compared to the traditional tumour grade. Methods: In total, 205 cases were investigated, and the Modified Bloom-Richardson score system was adopted in grading the tumours. The tissue sections of the cases were stained with specific primary antibodies at dilutions of 1:60 for oestrogen receptors (ER) and progesterone receptors (PR), 1:350 for the human epidermal growth factor (HER-2/neu) and 1:50 for p53. Results: Invasive ductal carcinoma of no-specific type (n = 190, 92.7%) was predominant and grade II tumour (n = 146, 71.2%) was the most frequent. Hormone receptors ER (n = 127) and PR (n = 145) had 62.0% and 70.7% positive cases, respectively; 34.1% (n = 70) were positive for HER-2/ neu, while 76.1% (n = 156) were positive for p53. Significant associations between Nottingham grade and expression patterns of ER (P &lt;0.01), PR (P &lt;0.001), HER-2/neu (P &lt;0.001) and p53 (P = 0.001) were observed. Conclusion: Nottingham grade had a high degree of concordance with the patterns of expression of hormone receptors, HER- 2/neu and p53, suggesting that it may play an important role in connection with the predictive and prognostic biomarkers for BC. Keywords: Breast Cancer; HER-2/neu; Heterogeneity; Hormone Receptor; Oncoprotein p53.

Performance and Interlaboratory Reproducibility of Droplet Digital Polymerase Chain Reaction (ddPCR) and Real Time PCR for KIT D816V Mutation Detection: A Nationwide Pilot Study By the RIMA (Rete Italiana Mastocitosi) Association

Systemic Mastocytosis (SM) is a rare hematological neoplasm, but its incidence is probably underestimated because of the heterogeneity of clinical symptoms and presentation that may cause diagnostic difficulties especially outside reference centers. Detection of the activating D816V KIT mutation in the bone marrow or peripheral blood is one of the minor criteria for the diagnosis of SM, but it poses some challenges since in the indolent forms (the most frequent) the mast cell burden is very low. For this reason, the National Comprehensive Cancer Network and the European Competence Network on Mastocytosis (ECNM) recommend a high-sensitivity PCR-based assay, such as Allele-Specific Oligonucleotide-Real Time Quantitative PCR (ASO-qPCR) or ddPCR, while Sanger and Next Generation Sequencing are considered not adequate. Accurate quantitation of allele burden (AB) is also desirable since it offers diagnostic (an AB³10% qualifies as a B-finding according to the latest WHO classification) and prognostic information and might be used to monitor response to tyrosine kinase inhibitors. Despite the widespread routine availability of real time and digital PCR technologies, a map of labs across Italy offering KIT D816V testing with adequate sensitivity is lacking, nor have cooperative efforts aimed to check lab performance and reproducibility of diagnostic results ever been performed. Based on these premises, RIMA undertook, with the sponsorship of the GIMEMA Working Party on Chronic Myeloproliferative Neoplasms, a project aimed to: i) build a nationwide network of competent reference laboratories performing KIT D816V mutation testing; ii) promote harmonization of local procedures and ensure adequate proficiency and cross-comparability of results. The pilot phase of this project involved 7 labs (L) spread across the country (Milan, Bologna, Verona, Florence, Rome, Naples, Pavia) serving one or more reference clinical centers for the diagnosis and management of SM. First, a survey aimed to assess the techniques and procedures in use in each participating lab was conducted. Five labs (L2-L6) used a commercial ddPCR assay (KIT p.D816V c.2447A&amp;gt;T, Assay ID dHsaCP2000023; Bio-Rad); one lab (L7) used a home brew ASO-qPCR assay; one lab (L1) used a commercial semi-quantitative real time PCR-based assay (PlentiPlex Mastocytosis D816V kit; Pentabase). All labs performed analyses in duplicate or triplicate using DNA as input material, with amounts variable from 50 to 250ng/replicate. Reported limit of detection (LoD) was 0.0003% for the home brew method and 0.01% for the commercial methods. Subsequently, a round robin test to evaluate and compare performance in terms of sensitivity and inter-lab reproducibility was carried out. Mutated and wild-type DNA isolated from HMC-1.2 and HL-60 cells, respectively, was mixed and diluted to mimic different D816V ABs, from 10% down to 0.01%. Dilutions were externally assessed by the UK Wessex Genomics Laboratory Service, using an accredited ddPCR assay with a limit of detection (LoD) of 0.01%. Of note, the sixth dilution (D6) was scored as slightly below their LoD (0.008%; 3 positive droplets only). Identical batches of blinded vials were then distributed and analyzed in parallel by the 7 participating labs according to their own routine protocols. Positivity/negativity as scored by L1-7 and AB values as scored by L2-7 are detailed in Table 1. All the evaluated methods proved highly accurate in the detection and, for ddPCR and ASO-qPCR, in the quantitation of the KIT D816V (R 2 between 0.988 and 0.998). A very high degree of concordance was achieved, for all dilutions, across different labs and methods (CV between 0.07 and 0.8). D6 was scored borderline by L1 and positive by all other labs. This pilot experience demonstrates that the evaluated PCR-based methods may reliably identify and quantitate the KIT D816V mutation down to an AB of 0.01% with a high degree of cross-comparability of results, thus assisting clinicians in the diagnosis and monitoring of SM patients. To the best of our knowledge, this is the first cooperative effort aimed to assess the performance and reproducibility of KIT D816V mutation testing in SM. Involvement of additional Italian labs is already planned, and further implementation within the ECNM will be proposed. Definition of common SOPs, uniform sample requirements and web-based reporting following the GIMEMA LabNet model will be pursued.