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INTRODUCTION: Personalized and tumor-informed circulating tumor DNA (ctDNA) testing is feasible and allows for molecular residual disease (MRD) identification in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: In this retrospective analysis of commercial cases from multiple US institutions, personalized, tumor-informed, whole-exome sequenced, and germline-controlled ctDNA levels were quantified and analyzed in patients with PDAC. Plasma samples (n = 1329) from 298 clinically validated patients were collected at diagnosis, perioperatively (MRD-window; within 2-12 weeks after surgery, before therapy), and during surveillance (>12 weeks post-surgery if no ACT or starting 4 weeks post-ACT) from November 2019 to March 2023. RESULTS: Of the initially diagnosed patients with stages I-III PDAC who went for resection, the median follow-up time from surgery was 13 months (range 0.1-214). Positive ctDNA detection rates were 29% (29/100) and 29.6% (45/152) during the MRD and surveillance windows, respectively. Positive ctDNA detection was significantly associated with shorter DFS within the MRD window (median DFS of 6.37 months for ctDNA-positive vs 33.31 months for ctDNA-negative patients; HR: 5.45, P

PURPOSE: Merkel cell carcinoma (MCC) is an aggressive skin cancer with a 40% recurrence rate, lacking effective prognostic biomarkers and surveillance methods. This prospective, multicenter, observational study aimed to evaluate circulating tumor DNA (ctDNA) as a biomarker for detecting MCC recurrence. METHODS: Plasma samples, clinical data, and imaging results were collected from 319 patients. A tumor-informed ctDNA assay was used for analysis. Patients were divided into discovery (167 patients) and validation (152 patients) cohorts. Diagnostic performance, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), was assessed. RESULTS: ctDNA showed high sensitivity, 95% (discovery; 95% CI, 87 to 99) and 94% (validation; 95% CI, 85 to 98), for detecting disease at enrollment, with corresponding specificities of 90% (95% CI, 82 to 95) and 86% (95% CI, 77 to 93). A positive ctDNA during surveillance indicated increased recurrence risk, with hazard ratios (HRs) of 6.8 (discovery; 95% CI, 2.9 to 16) and 20 (validation; 95% CI, 8.3 to 50). The PPV for clinical recurrence at 1 year after a positive ctDNA test was 69% (discovery; 95% CI, 32 to 91) and 94% (validation; 95% CI, 71 to 100), respectively. The NPV at 135 days after a negative ctDNA test was 94% (discovery; 95% CI, 90 to 97) and 93% (validation; 95% CI, 89 to 97), respectively. Patients positive for ctDNA within 4 months after treatment had higher rates of recurrence, with 1-year rates of 74% versus 21% (adjusted HR, 7.4 [95% CI, 2.7 to 20]). CONCLUSION: ctDNA testing exhibited high prognostic accuracy in detecting MCC recurrence, suggesting its potential to reduce frequent surveillance imaging. ctDNA also identifies high-risk patients who need more frequent imaging and may be best suited for adjuvant therapy trials.

Ditopic bis-pyrazolylpyridine ligands usually react with divalent metal ions (M2+) to produce dinuclear triple-stranded helicates [M2L3]4+ or, via π⋯π interactions, dimers of monoatomic complexes ([ML3]2)4+. The introduction of an additional benzene ring at each end of ligand L increases the number of aromatic contacts within the supramolecular aggregate by 40%, driving the self-recognition process in an irreversible manner. Consequently, the mixing of new bis-pyrazolylquinoline L2 with FeX2 salts leads to crystallization of the tripartite high-spin assemblies (X@[Fe(L2)3]2)3+ (X = Cl, Br or I). The aggregates exhibit exceptional stability, as confirmed by a combination of paramagnetic 1H NMR techniques, demonstrating their persistence in solution. Our investigations further reveal that the guests Br- and I- are retained inside the associate in solution but Cl- is immediately released, resulting in the formation of the empty supramolecular dimer ([Fe(L2)3]2)4+.

A wide range of the temperatures of hydrothermal fluid regime (430-103 °C) has been revealed in the result of microthermometric study of the fluid inclusions in the minerals of pre-ore and post-ore stages developed at the Elkon deposit. Average temperatures, as well as the temperature variation are similar for both pre-ore and post-ore stages. It allows sure determination of temperatures of uranium ore formation as 400-120 °C. Fluids possessed Na-chloride, rarely Na-chloride-carbonate composition and moderate salinity (6-16 wt. % · NaCl equiv.). The wide range of tem-peratures confirms an assumption made before that various temperatures were the reason of formation of uranium mineralization both in the form of predominantly amorphous phase (U-Ti-metagel), as well as the rarely crystalline form (brannerite). Abrupt temperature decrease was apparently the main factor of the ore precipitation.

Several studies have demonstrated the prognostic value of circulating tumor DNA (ctDNA); however, the correlation of mean tumor molecules (MTM)/ml of plasma and mean variant allele frequency (mVAF; %) with clinical parameters is yet to be understood. In this study, we analyzed ctDNA data in a pan‐cancer cohort of 23 543 patients who had ctDNA testing performed using a personalized, tumor‐informed assay (Signatera™, mPCR‐NGS assay). For ctDNA‐positive patients, the correlation between MTM/ml and mVAF was examined. Two subanalyses were performed: (a) to establish the association of ctDNA with tumor volume and (b) to assess the correlation between ctDNA dynamics and patient outcomes. On a global cohort, a positive correlation between MTM/ml and mVAF was observed. Among 18 426 patients with longitudinal ctDNA measurements, 13.3% had discordant trajectories between MTM/ml and mVAF at subsequent time points. In metastatic patients receiving immunotherapy (N = 51), changes in ctDNA levels expressed both in MTM/ml and mVAF showed a statistically significant association with progression‐free survival; however, the correlation with MTM/ml was numerically stronger.

Large-scale reserves of uranium in Au-U deposits of the Elkon ore district are composed of newly discovered polyphase uranium-titanium metagel (UTM). Before, it was assumed that brannerite is the major mineral of these ores. However, it has been revealed that brannerite and uranium oxides and silicates are minor components of mineralization. Succession of UTM phases selection, their relations with brannerite are characterized. Few groups of UTM has been revealed by composition of major and trace elements. The filter cake of acidic leaching of a technological sample with residual uranium concentration of 0,02 wt.% and grain size of -0.16 mm was investigated. As it was established, the major part of uranium is in the fine grained UTM phases submerged in quartz-feldspar matrix of the cake particles. Taking into account a small size of the uranium phases (first microns, rarely n-10 mkm), recrusing of the ore to smaller grades will unlikely lead to a noticeable uranium yield into final product.

We sought to investigate the feasibility of longitudinal monitoring of disease activity from home in people with hidradenitis suppurativa (HS). Over 6 months, our novel digital tool collected 421 photos of HS-affected skin from 27 participants and captured trends in pain and quality of life scores. We found that participants with mild disease were more likely to share their progress than those with more severe disease, which is favourable as it may suggest a role for remote monitoring in tracking disease progression. This pilot provides proof of concept that will support future studies.

AbstractThis study evaluated the accuracy of ChatGPT in translating English patient education materials into Spanish, Mandarin, and Russian. While ChatGPT shows promise for translating Spanish and Russian medical information, Mandarin translations require further refinement, highlighting the need for careful review of AI-generated translations before clinical use.

Circulating tumor DNA (ctDNA) analysis may improve early-stage breast cancer treatment via non-invasive tumor burden assessment. To investigate subtype-specific differences in the clinical significance and biology of ctDNA shedding, we perform serial personalized ctDNA analysis in hormone receptor (HR)-positive/HER2-negative breast cancer and triple-negative breast cancer (TNBC) patients receiving neoadjuvant chemotherapy (NAC) in the I-SPY2 trial. ctDNA positivity rates before, during, and after NAC are higher in TNBC than in HR-positive/HER2-negative breast cancer patients. Early clearance of ctDNA 3 weeks after treatment initiation predicts a favorable response to NAC in TNBC only. Whereas ctDNA positivity associates with reduced distant recurrence-free survival in both subtypes. Conversely, ctDNA negativity after NAC correlates with improved outcomes, even in patients with extensive residual cancer. Pretreatment tumor mRNA profiling reveals associations between ctDNA shedding and cell cycle and immune-associated signaling. On the basis of these findings, the I-SPY2 trial will prospectively test ctDNA for utility in redirecting therapy to improve response and prognosis.

BACKGROUND: In-hospital dermatological care has shifted from dedicated dermatology wards to consultation services, and some consulted patients may require postdischarge follow-up in outpatient dermatology. Safe and timely care transitions from inpatient-to-outpatient specialty care are critical for patient health, but communication around these transitions can be disjointed, and workflows can be complex. OBJECTIVE: In this 3-phase quality improvement effort, we developed and evaluated an intervention that leveraged an electronic health record (EHR) feature, known as SmartPhrase, to enable a new workflow to improve transitions from inpatient care to outpatient dermatology. METHODS: Phase 1 (February-March 2021) included interviews with patients and process mapping with key stakeholders to identify gaps and inform an intervention: a SmartPhrase table and associated workflow to promote collection of patient information needed for scheduling follow-up and closed-loop communication between dermatology and scheduling teams. In phase 2 (April-May 2021), semistructured interviews-with dermatologists (n=5), dermatology residents (n=5), and schedulers (n=6)-identified pain points and refinements. In phase 3, the intervention was evaluated by triangulating data from these interviews with measured changes in scheduling efficiency, visit completion, and messaging volume preimplementation (January-February 2021) and postimplementation (April-May 2021). RESULTS: Preintervention pain points included unclear workflow for care transitions, limited patient input in follow-up planning, multiple messaging channels (eg, EHR based, email, and phone messages), and time-inefficient patient tracking. The intervention addressed most pain points; interviewees reported the intervention was easy to adopt and improved scheduling efficiency, workload, and patient involvement. More visits were completed within the desired timeframe of 14 days after discharge during the postimplementation period (21/47, 45%) than the preimplementation period (28/41, 68%; P=.03). The messaging workload also decreased from 88 scheduling-related messages sent for 25 patients before implementation to 30 messages for 8 patients after implementation. CONCLUSIONS: Inpatient-to-outpatient specialty care transitions are complex and involve multiple stakeholders, thus requiring multifaceted solutions. With deliberate evaluation, broad stakeholder input, and iteration, we designed and implemented a successful solution using a standard EHR feature, SmartPhrase, integrated into a standardized workflow to improve the timeliness of posthospital specialty care and reduce workload.

Introduction. The standard of treatment for patients with single cerebral metastases is surgery and radiosurgery. The use of these methods significantly increases survival rates.Aim. To compare the results of surgical treatment of patients with single and multiple cerebral metastases.Materials and methods. The study included 40 patients with single and multiple cerebral metastases who underwent neurosurgical intervention in the neuro-oncology department of the N.N. Blokhin National Medical Oncology Research Center from 2010 to 2022.Results. All patients are divided into 3 groups. Group A included 15 patients who removed all available cerebral foci (from 2 to 4). Group B included 10 patients with multiple cerebral metastases who underwent removal of one symptomatic metastasis. In group C, 15 patients who underwent removal of a single metastasis. It was noted that the survival of patients after removal of all cerebral metastases is identical to the survival of patients after removal of single metastasis 11.9 and 12.4 months, respectively. And it was significantly higher than the survival of patients who removed not all cerebral metastases 6.2 months (p = 0.03). Also in group A and C, the percentage of local relapses was identical. Improvement in neurological status was noted in all groups, there was only an increase in cognitive-mnestic disorders in group A, where all cerebral foci were removed. However, these disorders were moderate and did not reach the extent of dementia. The work done shows.Conclusion. Surgical removal of all metastases in patients with multiple brain metastases provides a prognosis similar to that of patients undergoing surgery for single metastasis. Removal of symptomatic metastasis in patients with multiple cerebral lesions in most cases leads to a regression of neurological symptoms and makes it possible to continue treatment with a group of patients whose condition was considered incurable. The percentage of local relapses in the removal of multiple cerebral metastases, subject to oncological principles, is the same as in the removal of single metastases.

This study identifies similarities and differences in the structural organization and cultural attitudes expressed in Swedish and Russian proverbs of comparative semantics on poverty and wealth. It provides a classification of linguistic units (35 Swedish and 60 Russian proverbs) based on their expression of identity, comparison, contrast, and syntactic organization. The research reveals that in the Swedish language, proverbs expressing comparison with adjectives in the comparative degree have quantitative advantages, while in the Russian language, proverbs expressing contrast prevail. Similar cultural attitudes in Swedish and Russian proverbs of comparative semantics on poverty and wealth include:(1) The wealthy person’s material status is incomparably higher than that of the poor, but the poor person surpasses the wealthy in moral terms.(2) The wealthy always desire more, being unsatisfied with their wealth.(3) Laws operate differently for the rich and the poor.(4) Wealth is fleeting if not used wisely.Differences lie in specific cultural attitudes. For instance, Swedish proverbs focus on the wealthy person’s daughter as a coveted prize for those seeking easy enrichment, while Russian proverbs intensify certain qualities of individuals based on their degree of poverty / wealth (the poorer a person is, the more generous, wise, intelligent, brave, cunning they are, etc.).

В центре внимания – история застройки и заселения Адмиралтейского острова в Санкт-Петербурге в начале XVIII в. В ноябре 1704 г. была заложена Адмиралтейская верфь, которая к концу царствования Петра I превратилась в крупнейшее в России судостроительное предприятие. В историографии устоялось мнение, что первые жители острова были связаны с флотом и судостроением, однако социальная структура населения Адмиралтейского острова, организация на нем строительных работ и специфика административного управления до сих пор изучены фрагментарно. Основу источниковой базы исследования составили опубликованные и архивные материалы Адмиралтейской канцелярии и походной канцелярии Меншикова (переписка руководителей строительства и первые переписи строений), а также рукописные чертежи. Предложена новая датировка рукописного плана первоначального Адмиралтейства. Показано, что до учреждения Адмиралтейской канцелярии (1707) строительство на Адмиралтейском острове велось главным образом силами Адмиралтейского приказа, располагавшего кадрами мастеровых и работных людей. Петербургский обер-комендант Р. В. Брюс руководил работами по возведению Адмиралтейской крепости. За строительство промышленных, хозяйственных и жилых построек отвечал олонецкий комендант И. Я. Яковлев. Адмиралтейской остров стал первым в Санкт-Петербурге, на котором начали регламентировать застройку. В 1705 г. жилые дома и казармы на Адмиралтейском острове строились за счет казны и устанавливались в линии. Уже в первые годы сложилась система запретов и ограничений, призванная обеспечить безопасность от пожаров верфи и военно-морских судов как на Адмиралтейском, так и на Городском острове. В ходе исследования проанализировано содержание описей построек 1707 и 1711 г. Показано, что их появление было вызвано необходимостью контроля за выполнением мер противопожарной безопасности. Установлено, что в октябре 1707 г. служители Адмиралтейства переписывали постройки на Городском острове возле Кронверкской протоки. В результате анализа данных описи построек 1711 г. определено, что морским чинам принадлежало не менее 110 из 271 дворов. Особую ценность представляет то, что перепись была выполнена до переезда царского двора и правительства на берега Невы и до издания указов Петра I о мазанковом и каменном строительстве и регламентации застройки, изменивших облик первоначального Санкт-Петербурга.

For the logistic equation with diffusion two generalizations are considered: one with time delay and the other with deviation in the spatial variable. For these equations, the problem of density wave propagation is considered. These equations, known as Kolmogorov–Petrovsky–Piskunov–Fisher equations with delay or deviation (KPPF with delay or deviation), are investigated using both asymptotic and numerical methods.To investigate the qualitative behavior of solutions of such equations, the wave profile equation is considered and the conditions for the emergence of its oscillatory modes are identified.The local properties of solutions with periodic boundary conditions are examines, revealing that an increase in the period leads to the emergence of stable solutions with a more complex spatial structures.Numerical analysis of the wave propagation process indicates that at sufficiently small delay values, this equation has solutions that are close to those of the standard KPPF equation. Increasing the delay parameter leads first to the appearance of a damped oscillatory component in the spatial distribution of the solution. With further increases of this parameter, a complex spatial profile of the wave appears.In the final part of the chapter, which focuses on numerical calculation, the numerical analysis of the wave propagation process from two initial perturbations is performed. This analysis tracks the process of wave interaction. The complex spatially inhomogeneous structure that arises during wave propagation and interaction can be explained by the properties of the corresponding solutions of the periodic boundary value problem, especially as the interval of change in the spatial variable increases.

PurposeCirculating tumor DNA (ctDNA) analyses allow for postoperative risk stratification in patients with curatively treated colon and breast cancers. Use of ctDNA in esophagogastric cancers (EGC) is less characterized and could identify high-risk patients who have been treated with curative intent.MethodsIn this retrospective analysis of real-world data, ctDNA levels were analyzed in the preoperative, postoperative, and surveillance settings in patients with EGC using a personalized multiplex polymerase chain reaction-based next-generation sequencing assay. Plasma samples (n = 943) from 295 patients at > 70 institutions were collected before surgery, postoperatively, and/or serially during routine clinical follow-up from September 19, 2019, to February 21, 2022. ctDNA detection was annotated to clinicopathologic features and recurrence-free survival.ResultsA total of 295 patients with EGC were analyzed, and 212 patients with stages I-III disease were further explored. Pretreatment ctDNA was detected in 96% (23/24) of patients with preoperative time points. Postoperative ctDNA was detected in 23.5% (16/68) of patients with stage I-III EGC within 16 weeks (molecular residual disease window) after surgery without receiving systemic therapy. ctDNA detection at any time point after surgery (hazard ratio [HR], 23.6; 95% CI, 10.2 to 66.0; P < .0001), within the molecular residual disease window (HR, 10.7; 95% CI, 4.3 to 29.3; P < .0001), and during the surveillance period (HR, 17.7; 95% CI, 7.3 to 50.7; P < .0001) was associated with shorter recurrence-free survival. In multivariable analysis, ctDNA status and clinical stage of disease were independently associated with outcomes.ConclusionUsing real-world data, we demonstrate that postoperative tumor-informed ctDNA detection in EGC is feasible and allows for enhanced patient risk stratification and prognostication during curative-intent therapy.

Chl-a concentration is one of the key characteristics of marine areas related to photosynthesis, along with oxygen levels and water salinity. Most studies focus on estimating chl-a concentration in closed water bodies, rivers, and coastal areas of the tropical and temperate Earth belts and are therefore limited to specific regions and also require direct measurements and chemical analysis to obtain precise information about marine environmental conditions. Remote sensing techniques and spatial modeling aim to offer tools for rapid and global analysis of climate and ecological changes. In this study, we aim to develop a machine learning (ML)-based approach to estimate chlorophyll-a concentration when satellite data are unavailable. To provide physical parameters that may influence the predicted variable (chl-a concentration), we combined satellite observations from MODIS with geophysical Weather Research & Forecasting (WRF) and Nucleus for European Modelling of the Ocean (NEMO) models. Classical ML and deep learning (DL) algorithms were compared and analyzed for their ability to extract key biogeochemical patterns in the Barents Sea. The proposed approach allows us to forecast chl-a concentration for the next 8 days based on spatial features and measurements from preceding days. The best R2 metric achieved was 0.578 using a LightGBM algorithm, confirming the applicability of the developed solution to map the northern marine region even in cases where MODIS observations are unavailable for the preceding period due to insufficient illumination and dense cloud cover.

Interventional examinations are associated with high levels of patient exposure per examination, which makes it particularly important to monitor individual patient doses and to assess radiation risks. The aim of this study was the assessment of effective doses for fluoroscopy-guided balloon dilatation of benign esophageal strictures, whichwasperformedonpediatricpatientsaged 1 to 2 yearsatthe Departmentof Radiosurgical Methodsof Diagnosis and Treatment of St. Petersburg State Pediatric Medical University. Patient exposure patterns were basedonourowndatacollection. Thecalculationofeffectiveandorgandosesofpatientsnormalizedbythevalue of the dose area product measured during the study was carried out using PCXMC 2.0 software. The conversion coefficients from the dose area product to the effective dose were calculated using tissue weighting coefficients from the ICRP Publications 60 and 103 their values were 10.7 and 11.7 µSv/cGy cm2, respectively. The results of verification of the method indicated that the use of inappropriate conversion coefficients leads to an almost double underestimation of children’s effective doses. Differences in the values of conversion coefficients are significant and are explained by differences in voltage, source to image distance, and irradiation field size. A simplified model of patient exposure was proposed, which is described by a single irradiation field. The assessment of effective doses using multi-field and single-field irradiation model shows comparable results, which allows using the differentiated approach to the assessment of radiation doses of patients.

Research and development of power factor corrector (PFC) for AC/DC converters of single-phase AC power supply network are discussed within this article. Two-channel bridgeless PFC is proposed in this paper. The proposed converter allows us to lower current DC component generation in the power network and to reduce static and dynamic losses of semiconductor devices. The suggested solution characteristic features are the absence of a diode bridge while using two identical converters operating in different power network voltage half periods. Due to cumulative chokes in each converter, the function setting the consumption current sinusoidal form is realized with the ability of wide-range output voltage regulation. A number of Simulink-models have been developed in order to study operating modes and to test control algorithms of the proposed bridgeless PFC. The input current harmonic content, efficiency coefficient, passive elements’ electrical parameters, and output voltage pulsation coefficient of the proposed bridgeless PFC were researched by Simulink-models. The results obtained show the efficiency of the proposed solutions regarding PFC. The THD value does not exceed 1.3% in steady state mode and is not over 4% during the voltage stabilization process; the minimal value of the output voltage pulsation coefficient is 3.1%. The suggested solutions can be applied in accumulator batteries’ charging sets and DC motors’ reduced-current start.