Analysis Method Research Articles

Peripartum allopregnanolone blood concentrations and depressive symptoms: a systematic review and individual participant data meta-analysis

AbstractNeuroactive steroids including allopregnanolone are implicated in the pathophysiology of peripartum depressive symptoms (PDS). We performed a systematic review searching PubMed/Embase/PsychInfo/Cinhail through 08/2023 (updated in 07/2024), and conducted a random-effects meta-analysis of studies comparing allopregnanolone blood concentrations in women with versus without PDS at various timepoints during the 2nd and 3rd trimester and the postpartum period, calculating standardized mean differences (SMDs) and 95% confidence intervals (CIs). Meta-regression and subgroup analyses included age, diagnoses of affective disorders before pregnancy, antidepressant treatment, analytical methods, and sample type. Study quality was assessed using the Newcastle-Ottawa-scale. The study protocol was registered on PROSPERO (registration number CRD42022354495). We retrieved 13 studies with 2509 women (n = 849 with PDS). Allopregnanolone concentrations did not differ between women with versus without PDS at any timepoint (p > 0.05). Allopregnanolone concentrations assessed during pregnancy did not differ for women with versus without PDS at postpartum follow-up (p > 0.05). Subgroup analyses indicated higher allopregnanolone concentrations in women with versus without PDS at gestational weeks 21–24 and 25–28 (SMD = 1.07, 95% CI = 0.04, 2.11 and SMD = 0.92, 95% CI = 0.26, 1.59 respectively). Moreover, we reported differences between studies using mass-spectrometry combined with chromatography versus immunoassays at gestational weeks 25–28 (p = 0.01) and plasma versus serum samples at gestational weeks 21–24 (p = 0.005). Study quality was rated as poor, good, and fair for two, one and ten studies respectively. PDS were not associated with differences for allopregnanolone concentrations. The use of heterogenous peripartum time points, study cohorts, depression symptom measures and analytical methods has hampered progress in elucidating neuroactive steroid signaling linked to PDS.

Retraction Note: Obtaining optical soliton solutions of the cubic–quartic Fokas–Lenells equation via three different analytical methods

Retraction Note: Obtaining optical soliton solutions of the cubic–quartic Fokas–Lenells equation via three different analytical methods

Influence of physico-chemical properties of hydroxypropyl methylcellulose on quetiapine fumarate release from sustained release matrix tablets

Quetiapine fumarateis a typical antipsychotic with a short half-life of 6 h and is administered multiple times daily. In this study, a copolymer for controlled delivery of quetiapine fumarate will be developed. In order to prevent side effects and improve patient compliance, hydroxypropyl methylcellulose K15M (HPMC K15M) was included in the formulation of the quetiapine fumarate oral sustained-release tablets at a concentration of 10–30%. A series of analytical methods were used to determine the characteristics of the prepared hydrogels, including Fourier transform-infrared spectroscopy, Differential scanning calorimetry, X-ray diffraction, and Scanning electron microscope. At two different pH values (1.2 and 6.8), swelling and release studies were conducted. A variety of release kinetic models was used to study drug release mechanisms. A non-Fickian diffusion mechanism released hydrogels prepared from quetiapine fumarate. It was found that swelling was increased by increasing the amount of HPMC K15M. Compared to the other batches (10–20%), the produced tablets with 30% HPMC K15M content had a better release profile after 20 h of dissolution. Because of the effective matrix complex’s limited solubility in water, the drug diffuses through the gel layer at a steady rate rather than dissolving quickly.

Implemention of Innovative Process Analytical Technologies to Characterize Critical Quality Attributes of Co‐Formulated Monoclonal Antibody Products

ABSTRACTCharacterizing co‐formulated monoclonal antibodies (mAbs) poses significant challenges in the pharmaceutical industry. Due to the high structural similarity of the mAbs, traditional analytical methods, compounded by the lengthy method development process, hinder product development and manufacturing efficiency. There is increasing critical need in the pharmaceutical industry to streamline analytical approaches, minimizing time and resources, ensuring a rapid clinical entry and cost‐effective manufacturing. This study investigates the application of process analytical technologies (PAT) to address such challenges. Our investigation introduces two complementary technologies, on‐line ultra‐performance liquid chromatography (online UPLC) and multimode fluorescence spectroscopy (MMFS), as potential PAT tools tailored for characterizing critical quality attributes (CQA) in co‐formulated mAb products. Specifically, the CQAs under evaluation include the total protein concentration of the mAbs within the co‐formulation and the ratio of mAb A to mAb B. Online UPLC enables direct and automated measurement of the CQAs through physical separation, while MMFS determines them in a non‐destructive and more swift manner based on chemometric modeling. We demonstrate these technologies' comparable performance to conventional methods, alongside substantial benefits such as reduced analytical turnaround time and decreased laboratory efforts. Ultimately, integrating them as innovative PAT tools expedites the delivery of therapeutic solutions to patients and enhances manufacturing efficiency, aligning with the imperative for swift translation of scientific discoveries into clinical benefits.

Exploiting the diversity of modeling methods to probe systematic biases in strong lensing analyses

Challenges inherent to high-resolution and high signal-to-noise data as well as model degeneracies can cause systematic biases in analyses of strong lens systems. In the past decade, the number of lens modeling methods has significantly increased, from purely analytical methods, to pixelated and non-parametric ones, or ones based on deep learning. We embraced this diversity by selecting different software packages and use them to blindly model independently simulated Hubble Space Telescope (HST) imaging data. To overcome the difficulties arising from using different codes and conventions, we used the COde-independent Organized LEns STandard (COOLEST) to store, compare, and release all models in a self-consistent and human-readable manner. From an ensemble of six modeling methods, we studied the recovery of the lens potential parameters and properties of the reconstructed source. In particular, we simulated and inferred parameters of an elliptical power-law mass distribution embedded in a shear field for the lens, while each modeling method reconstructs the source differently. We find that, overall, both lens and source properties are recovered reasonably well, but systematic biases arise in all methods. Interestingly, we do not observe that a single method is significantly more accurate than others, and the amount of bias largely depends on the specific lens or source property of interest. By combining posterior distributions from individual methods using equal weights, the maximal systematic biases on lens model parameters inferred from individual models are reduced by a factor of 5.4 on average. We investigated a selection of modeling effects that partly explain the observed biases, such as the cuspy nature of the background source and the accuracy of the point spread function. This work introduces, for the first time, a generic framework to compare and ease the combination of models obtained from different codes and methods, which will be key to retain accuracy in future strong lensing analyses.

Children’s Diets and Planetary Health: A Study in Wroclaw, Poland, and Sydney, Australia

Meals served to children should not only satisfy hunger and taste preferences but also be nutritionally adequate. Nutrition in early childhood is critical, as children spend a significant portion of their day in kindergarten or preschool, making these settings key contributors to their overall dietary intake. With the rising prevalence of nutrition-related health conditions among children, early interventions are essential for developing and establishing lifelong healthy eating habits. This study assessed the nutritional value and quality of children’s diets in two distinct settings: kindergartens in Wroclaw, Poland, and preschools in Sydney, Australia, evaluating their alignment with the planetary health diet. The research analysed 10-day menu cycles from five kindergartens in Wroclaw and the contents of lunchboxes from five preschools in Sydney’s Upper North Shore area. A total of 100 menus were reviewed in Poland, while 100 children’s lunchboxes were assessed in Australia. Different analytical methods were employed: the Diet 6D software program for the Polish menus and the Food Consumption Score for the Australian lunchboxes. Both methods revealed dietary imbalances, such as excessive intake of protein, vitamin A, salt, and sugar, alongside deficiencies in calcium, vitamin C, and vitamin D. The study concluded that children’s diets should adhere to nutritional guidelines, meeting both Polish and Australian standards, and align with the principles of the planetary health diet. To achieve this, nutritional education is essential for kindergarten staff in Poland, while targeted educational interventions are needed for parents and children in both Poland and Australia, promoting health and environmental sustainability through better nutrition.

A Review of Principles, Analytical Methods, and Applications of SEM‐EDS in Cementitious Materials Characterization

AbstractScanning Electron Microscopy with Energy Dispersive Spectroscopy (SEM‐EDS) is an indispensable and versatile technique that provides detailed 2D spatial insights into the microstructure of heterogenous cementitious systems. To foster clear and systematic understanding of SEM‐EDS analysis in advancing research on cementitious materials, the state‐of‐the‐art principles, analytical approaches, and applications of SEM‐EDS analysis in cementitious systems are reviewed. This review aims to assist researchers in selecting the most appropriate strategy for SEM‐EDS analysis to quantify phase assemblage, elucidate environmental interactions, and investigate microstructure evolution in cementitious systems. The fundamental concepts related to equipment, signal generation, acquisition of diverse EDS data are first presented. Subsequently, various analysis approaches, including point analysis, grid analysis, and mapping analysis are discussed. This review then emphasizes the practical significance and potential value of SEM‐EDS analysis in addressing phase quantification challenges pertaining to cementitious systems. It is posited that the SEM‐EDS analysis holds the promise of becoming the characterization backbone for quantitative research on cementitious systems.

Bi-Stable Metamaterials with Intrinsic Memory for Selective Wave Filtering Based on Frequency and Amplitude.

Analytical, numerical, and experimental methods are used to investigate the utility of metamaterials in controlling harmonic waves based on both their amplitude and frequency. By programming the metamaterials to support bi-stable configurations (i.e., two stable phases), the required conditions are elucidated for a transition wave (i.e., a topological soliton) to nucleate due to harmonic excitation, causing a phase change within ourmetamaterial. As each of these phases has its own unique transmission frequency range, such phase change is harnessed to control harmonic waves based on both their amplitude and frequency. As a demonstration of principle, a low/high-pass filter is shown by tuning the same metamaterial to change phase; from transmission to attenuation and vice versa. In addition, phase transitions taking place while preserving the metamaterial's state of attenuation or transmission are shown. Such materials can continue their functionality (i.e., either attenuation or transmission of waves) while keeping a record of extreme events that can cause their transition (i.e., have memory). These metamaterials can be useful in the next generations of advanced and functional acoustic devices.

Einstein’s spacetime curvature and gravitational waves: Elucidating the gradient flow of scalar invariants, variations in the Ricci scalar, and gravitational wave propagation

In the general theory of relativity initially rationalized by Einstein, the gravity is considered as an occurrence ensuing from the spacetime curvature, which is in turn triggered by the presence of mass. This article provides a detailed analysis of spacetime curvature and gravitational waves, enhancing our understanding of general relativity and astrophysics. Using both analytical and numerical methods, we examined the gradient flow of scalar invariants, variations in the Ricci scalar, and gravitational wave propagation. New findings include the identification of unique curvature patterns around rotating black holes, a detailed comparison of gradient flow behavior in different spacetime geometries, and the discovery of a correlation between scalar invariant fluctuations and gravitational wave amplitudes. These findings validate numerical techniques and reveal how different parameters affect gravitational wave characteristics. While simplified models are used, the present study offers a robust framework for future research. Our work aligns with previous studies but also reveals unique aspects of wave behavior, with implications for quantum gravity and cosmology.

Application of Digital Technology for Oil and Gas Fields

The paper investigates the problem of isothermal filtration using an approximate method for solving the theory of partial differential equations. The mathematical model under consideration is nonlinear and does not lend itself to analytical methods of solution. The results obtained indicate the need for wide application in the development of oil and gas fields in the Republic of Kazakhstan. In particular, the results of the study make it possible to solve the problems of adapting mathematical models and evaluating changes in technological indicators, which are necessary attributes in the digital technology ""Information System for the Analysis of oil and Gas Field Development"" (ISAR). Many problems and mathematical problems of filtration theory arose while working on specific oil and gas fields in the western region of the Republic of Kazakhstan. The above approximate solution methods have found applications not only in filtration theory, but also in other problems (geophysics, ecology, etc.)"

A framework to model charge sharing and pulse pileup for virtual imaging trials of photon-counting CT

Objective.This study describes the development, validation, and integration of a detector response model that accounts for the combined effects of x-ray crosstalk, charge sharing, and pulse pileup in photon-counting detectors.Approach.The x-ray photon transport was simulated using Geant4, followed by analytical charge sharing simulation in MATLAB. The analytical simulation models charge clouds with Gaussian-distributed charge densities, which are projected on a 3×3 pixel neighborhood of interaction location to compute detected counts. For pulse pileup, a prior analytical method for redistribution of energy-binned counts was implemented for delta pulses. The x-ray photon transport and charge sharing components were validated using experimental data acquired on the CdTe-based Pixirad-1/Pixie-III detector using monoenergetic beams at 26, 33, 37, and 50 keV. The pulse pileup implementation was verified with a comparable Monte Carlo simulation. The model output without pulse pileup was used to generate spatio-energetic response matrices for efficient simulation of scanner-specific photon-counting CT (PCCT) images with DukeSim, with pulse pileup modeled as a post-processing step on simulated projections. For analysis, images for the Gammex multi-energy phantom and the XCAT chest phantom were simulated at 120 kV, both with and without pulse pileup for a range of doses (27-1344 mAs). The XCAT images were evaluated qualitatively at 120 mAs, while images for the Gammex phantom were evaluated quantitatively for all doses using measurements of attenuation coefficients and Calcium concentrations.Main results.Reasonable agreement was observed between simulated and experimental spectra with Mean Absolute Percentage Error Values (MAPE) between 10%and 31%across all incident energies and detector modes. The increased pulse pileup from increased dose affected attenuation coefficients and calcium concentrations, with an effect on calcium quantification as high as MAPE of 28%.Significance.The presented approach demonstrates the viability of the model for enabling VITs to assess and optimize the clinical performance of PCCT.

Rapid Assessment Method of Buckling Stability of Bridge Pier–Cap–Pile System Under Scour Effect

A novel analytical method for evaluating the buckling stability of the pier–cap–pile system under scour effect is proposed, and furthermore, the concept of rapid assessment of bridge buckling stability based on natural frequency is innovatively introduced in this paper. First, the total potential energy function of the bridge pier–cap–pile system is established, and the closed-form solution of structural system critical buckling load under scouring is solved according to the principle of stationary potential energy. Second, the sensitivity analyses of pier height, pier width, bending stiffness reduction in pier, pile slenderness ratio, pile bending stiffness reduction, m-value of soil and structural gravity to the buckling load are carried out. On this basis, 60 sets of sensitive parameter sample combinations are extracted by the Latin Hypercube Sampling algorithm, and a proxy model relating the critical buckling load to scour depth and the sensitive parameters are then developed using the McQuarter global optimization algorithm. Finally, the regression relationship model between the critical buckling load and the natural frequency is formed by combining the proxy model and the existing relationship between the scour depth and the first-order natural frequency. The feasibility of the proposed assessment method is demonstrated by the finite element method using a bridge case study, which provides an insight and a new means of quantitatively evaluating the safety of bridges under scour effect.

A detailed analysis of game statistics of professional tennis players: An inferential and machine learning approach.

Tennis, a widely enjoyed sport, motivates athletes and coaches to optimize training for competitive success. This retrospective predictive study examines anthropometric features and statistics of 1990 tennis players in the 2022 season, using 20,040 data points retrospectively obtained from the ATP official source after the end of the season. These data were cross-verified with information from other sources before categorisation to address any discrepancies. Employing various analytical methods, the results emphasize the strategic importance of tournament participation and gameplay for financial gains and higher rankings. Prize money analysis reveals a significant disparity favoring top players. Multivariate Analysis of Variance highlights the need to consider multiple variables for understanding ATP rankings. Multinomial Logistic Regression identifies age, height, and specific service-related metrics as key determinants, with older and taller players more likely to secure top positions. Neural Network models exhibit potential in predicting ATP Rank outcomes, particularly for ATP Rank (500). Our results argue for the use of Artificial Intelligence (AI), specifically Neural Networks, in handling complex interactions and emphasize that AI is a supportive tool in decision-making, requiring careful consideration by experienced individuals. In summary, this study enhances our understanding of ATP ranking factors, providing actionable insights for coaches, players, and stakeholders in the tennis community.

Application of computational algorithms for single-cell RNA-seq and ATAC-seq in neurodegenerative diseases.

Recent advancements in single-cell technologies, including single-cell RNA sequencing (scRNA-seq) and Assay for Transposase-Accessible Chromatin using sequencing (scATAC-seq), have greatly improved our insight into the epigenomic landscapes across various biological contexts and diseases. This paper reviews key computational tools and machine learning approaches that integrate scRNA-seq and scATAC-seq data to facilitate the alignment of transcriptomic data with chromatin accessibility profiles. Applying these integrated single-cell technologies in neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, reveals how changes in chromatin accessibility and gene expression can illuminate pathogenic mechanisms and identify potential therapeutic targets. Despite facing challenges like data sparsity and computational demands, ongoing enhancements in scATAC-seq and scRNA-seq technologies, along with better analytical methods, continue to expand their applications. These advancements promise to revolutionize our approach to medical research and clinical diagnostics, offering a comprehensive view of cellular function and disease pathology.

The Effect of Cryogenic Treatment on a High Co Bearing DIN 1.2888 Steel Used as Die in Hot Forging Process

Abstract Hot work steels used as dies in metal forming processes must endure harsh conditions, typically achieved through a martensitic structure. However, retained austenite can persist after martensitic transformation, negatively impacting mechanical properties. Cryogenic treatment (CT) refines martensite, reduces retained austenite, and increases fine carbide density, thus enhancing performance. DIN 1.2888, a hot work tool steel with high cobalt content (~10%) and low carbon content (~0.2%), is less studied concerning the effects of CT. The objective of this study was to investigate how cryogenic treatment affects the mechanical and microstructural properties of DIN 1.2888 steel. Samples underwent conventional heat treatment (HT) and CT at -100, -140, and -180°C for 6 hours, followed by double tempering. Various analytical methods, including X-ray diffraction (XRD), scanning electron microscopy with energy-dispersive X-ray spectroscopy (SEM-EDS), and Vickers Microhardness tests, were used to examine the samples. Wear mechanisms were evaluated through pin-on-disc tests under different loads, and impact toughness was measured both at room temperature and the working temperature of dies (350°C). Results indicated that lowering the cryogenic treatment temperature resulted in a slight increase in hardness values from 507HV for the heat-treated sample to 529HV for the sample treated at -180°C. Additionally, the impact toughness improved significantly, with values rising from 12.35J for the heat-treated sample to 23.44J at 350°C for the cryogenically treated sample at -180°C. Wear rates also decreased by approximately 50%, particularly at higher cryogenic treatment temperatures. The improvement in wear resistance was attributed to finer carbide precipitation and a more homogeneous distribution of carbides. These findings suggest that deep cryogenic treatment has a positive effect on DIN 1.2888 steel by decreasing retained austenite and increasing fine carbide density, leading to enhanced mechanical properties and extending the lifespan of the steel in die applications.

Analytical Characteristics and Clinical Performance of Anti-Müllerian Hormone Immunoassay on the ADVIA Centaur® System: A Comparison with Other Chemiluminescent Methods

Background: Serum anti-Müllerian hormone (AMH) levels and antral follicle count are key in evaluating ovarian reserve (OR) for fertility. The performance of the Siemens Healthineers AMH assay was assessed on the ADVIA Centaur® System. Methods: Analytical characteristics, clinical performance, and method comparison studies were performed in a prospective cohort of 532 women at fertility clinics. Serum AMH levels were determined using ADVIA Centaur, Beckman Access®, and Roche Elecsys® assays. Results: The limit of quantitation for the ADVIA Centaur AMH assay was 0.030 ng/mL. Repeatability was ≤2.9% CV, within-lab repeatability was ≤3.2% CV, and reproducibility was ≤4.4% CV. Results using serum or lithium heparin sample types were equivalent. Diagnostic sensitivity across assays ranged from 77.3% to 90.2% and specificity ranged from 51.0 to 71.0%; corresponding positive and negative predictive values ranged from 66.6% to 74.3% and 74.2% to 83.0%, respectively. Receiver operating characteristic analyses demonstrated that the assays have a high probability for discriminating between diminished–normal and high OR. ADVIA and Beckman assays agreed according to ADVIA = 1.00 × Beckman + 0.014 ng/mL, τ = 0.909, while a more modest correlation of ADVIA = 1.41 × Roche − 0.024 ng/mL, τ = 0.777 was observed with Roche assay. Conclusions: The ADVIA Centaur assay demonstrates acceptable analytical characteristics and clinical performance comparable to the Roche AMH assay and is essentially interchangeable with the Beckman AMH assay for reliable OR assessment.

Compensation to Ex-Wives for Domestic Violence in Indonesia

This paper examines divorce lawsuits caused by domestic violence committed by husbands against wives, focusing on the rights of women as victims. In such cases, wives can file for divorce and demand compensation for the physical and psychological harm they have suffered. The study employs a qualitative approach with an analytical descriptive method, using the library method to gather and analyze both primary and secondary literature, including legal documents, laws, scientific articles, and case reports. The research aims to identify patterns, challenges, and solutions related to legal protection for victims of domestic violence in divorce proceedings. The findings reveal that while there are legal provisions for compensation, significant challenges remain, such as social stigma, economic dependence, and limited access to legal resources, which complicate women's ability to claim their rights. Additionally, societal attitudes and gaps in law enforcement further hinder the realization of justice for victims. The study concludes that public awareness campaigns and stronger advocacy are essential to empowering women and ensuring their rights are protected throughout the divorce process. It also emphasizes the need for stricter law enforcement to hold perpetrators accountable and provide justice for victims. This research contributes to improving legal and social frameworks for the protection of women facing domestic violence.

The Impact of Socialization on Political Participation in Jordan (1989-2015)

Objectives: The study aimed to show the reality and influence of socialization on political participation from the point view of Political party leaders in Jordan. Methods: The study in order to measuring the level of influence of socialization and find the degree of participation, used the descriptive analytical method to analyze the data collected through a refereed scientific questionnaire targeted the active party leaders and party figures in Jordan, consisting of (297) selected as a random sample Results: The study findings were, a medium degree of approval among party leaders and figures on the reality of socialization, a medium degree of approval on the reality of political participation and the presence of a statistically significant effect of socialization on political participation explains a percentage of (57.6%). And from the variation in political participation indicates that the extent of the clear impact of socialization on the process of political participation in Jordan. Conclusions: The study concluded that there is a need to work to raise the level of political awareness among young people in society, and the political parties must work on formulating and preparing integrated programs with clear goals and vision in order to attract the target group and participation within it in political future work in Jordan. That can be achieved only by moving to actual work, and activating the role of various governmental institutions, agencies and community organizations in spreading awareness of political culture among young people through educational, media, cultural and partisan institutions.

Extraction of methamphetamine and pseudoephedrine by modified graphene oxide solid phase extraction method coupled to HPLC-UV in urine sample.

Methamphetamine, pseudoephedrine, and related drugs are among the first drugs used for the stimulation of the central nervous system. In this study, two adsorbents based on graphene oxide (GO) were synthesized and used for the analysis of methamphetamine and pseudoephedrine. The prepared nano-adsorbents based on GO in this study were coated by polyaniline (PANI) and Fe3O4/C-nanodot/GO (magnetic adsorbent). The average size of nanoparticles (GO/PANI) was 18.43nm. The specific surface area and pore size diameter of Fe3O4/C-nanodot/GO were 22.71 m2 g- 1 and 15.23nm, respectively. Experimental variables affecting the extraction efficiency of the analytes such as pH of the sample solution, amount of adsorbent, extraction time, and type of eluents were investigated and optimized by response surface methodology. Under optimum conditions, GO/PANI and Fe3O4/C-nanodot/GO were considered appropriate solid phase extraction adsorbents for HPLC-based analyses of the studied drugs in human urine samples. However, GO/Fe3O4 nano adsorbent (Fe3O4/C-nanodot/GO) showed superior working condition than GO/PANI. The validated proposed analytical methods can be used for the quantitative determination of methamphetamine and pseudoephedrine in actual samples.

Motivations of Israeli physicians to return, or not, to Israel after their fellowship abroad.

Emigration of healthcare professionals, particularly physicians, is an unresolved "pandemic", influenced by various factors. In high-income countries, the training phase (fellowship) abroad is critical for career development, yet it poses challenges for the retention of these professionals upon their completion of training. This study aimed to identify the determinants influencing Israeli physicians' decisions to return to their home country after completing fellowship training abroad. This cross-sectional study conducted in early 2024, surveyed Israeli physicians with post-graduate training who pursued a fellowship abroad between 2013 and 2024. An anonymous survey included questions on demographics, training experience, and professional challenges. Analytical methods included descriptive statistics and regression analysis to explore factors associated with the decision to return. Of the 323 individuals surveyed, 297 met the inclusion criteria. Among them, 141 (47.5%) have returned to Israel, while 156 (52.5%) currently reside abroad, 48 (31%) of them have completed their fellowship. Respondents identified several challenges, beginning with a complex application process prior to fellowship (47% stated this as a major challenge), substantial financial burdens averaging 35,546 USD in direct out-of-pocket expenses during, and job uncertainty, with only 55% having secured positions upon return. Of the 156 Israeli fellows still abroad, 107 (69%) reported medium to low confidence in returning. Factors associated with a higher likelihood of confidence in returning to Israel included a secured job position upon return (OR 8.6, 95% CI 3.1-28.9) and having an opportunity for a position that would utilize the skills gained during the fellowship (OR 3.5, 95% CI 1.3-10.2). The decision to return to Israel after a fellowship abroad is influenced by a mix of professional, personal, and geopolitical factors. To counteract the critical issue of brain drain, it is essential to enhance occupational certainty for returning physicians. These findings highlight the urgent need for healthcare policies that provide robust support for returning professionals and address their specific challenges.