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In cooperative multi-agent reinforcement learning, agents jointly optimize a centralized value function based on the rewards shared by all agents and learn decentralized policies through value function decomposition. Although such a learning framework is considered effective, estimating individual contribution from the rewards, which is essential for learning highly cooperative behaviors, is difficult. In addition, it becomes more challenging when reinforcement and punishment, help in increasing or decreasing the specific behaviors of agents, coexist because the processes of maximizing reinforcement and minimizing punishment can often conflict in practice. This study proposes a novel exploration scheme called multi-agent decomposed reward-based exploration (MuDE), which preferably explores the action spaces associated with positive sub-rewards based on a modified reward decomposition scheme, thus effectively exploring action spaces not reachable by existing exploration schemes. We evaluate MuDE with a challenging set of StarCraft II micromanagement and modified predator-prey tasks extended to include reinforcement and punishment. The results show that MuDE accurately estimates sub-rewards and outperforms state-of-the-art approaches in both convergence speed and win rates.
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BACKGROUND: The escalating utilization of assisted reproductive technology (ART) in response to global infertility rates has spurred research into its complications. Short-term and long-term outcomes have been extensively studied, particularly the neurological concerns surrounding attention-deficit/hyperactivity disorder (ADHD) among ART-conceived children. This study aims investigate the association between ART and ADHD. METHODS: Medline, Embase, Scopus, and Web of Science databases were searched through April 4, 2023. Cohort, case-control, and cross-sectional studies were eligible for inclusion. primary summary measures included the unadjusted relative risk (RR) and adjusted hazard ratio (HR) with 95â¯% confidence intervals. Both fixed-effects and random-effects models were utilized for meta-analysis data pooling to determine the overall effect size. The onset of ADHD in children conceived through ART compared to those conceived naturally. RESULTS: The systematic search yielded 8 studies with 10,176,148 individuals included in the meta-analysis. The meta-analysis revealed a pooled RR of 0.93 (0.68-1.26) for cohort studies and a pooled RR of 0.97 (0.41-2.29) for cross-sectional studies, along with a pooled HR of 1.08 (1.03-1.13) for ADHD in the ART group compared to the non-ART group. CONCLUSION: While this study identifies some potential association between ART and ADHD, the limited effect size and inherent heterogeneity underscore the need for cautious interpretation.
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Monitoring mosquito populations is essential for controlling mosquito-borne diseases, and the selection of mosquito traps should be tailored to specific surveillance objectives. Here, we tested four mosquito traps for their efficiency and applicability: the Nozawa-style black light trap (BLT), BG-sentinel trap II (BGT), UV-LED Blackhole Plus Mosquito Buster trap (LED), and digital mosquito monitoring system (DMS). The traps were rotated weekly for a 24 h cycle at the same location for 13 weeks. Overall, 1649 female mosquitoes belonging to seven genera and sixteen species were collected by the traps. The traps exhibited differences in both the number of collected individuals and species composition. The BLT showed superior collection efficiency in terms of the number of collected individuals and species evenness, whereas the BGT showed the highest species diversity among all the traps. Thus, the BLT and BGT are the best choices for effective mosquito surveillance based on trap performance. Additionally, despite the relatively low efficiency of the LED and DMS observed in this study, the LED is known to be efficient when used for indoor conditions such as cowsheds, while the DMS has an advanced function that can automatically count the number of mosquitoes. Thus, our findings provide significant guidelines for planning new mosquito surveillance projects in the ROK.
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B-cell-lymphoma-2 (BCL2) homology-3 (BH3) mimetics are inhibitors of protein-protein interactions (PPIs) that saturate anti-apoptotic proteins in the BCL2 family to induce apoptosis in cancer cells. Despite the success of the BH3-mimetic ABT-199 for the treatment of haematological malignancies, only a fraction of patients respond to the drug and most patients eventually develop resistance to it. Here we show that the efficacy of ABT-199 can be predicted by profiling the rewired status of the PPI network of the BCL2 family via single-molecule pull-down and co-immunoprecipitation to quantify more than 20 types of PPI from a total of only 1.2 × 106 cells per sample. By comparing the obtained multidimensional data with BH3-mimetic efficacies determined ex vivo, we constructed a model for predicting the efficacy of ABT-199 that designates two complexes of the BCL2 protein family as the primary mediators of drug effectiveness and resistance, and applied it to prospectively assist therapeutic decision-making for patients with acute myeloid leukaemia. The characterization of PPI complexes in clinical specimens opens up opportunities for individualized protein-complex-targeting therapies.
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The difluoromethyl group (CF2H) serves as an essential bioisostere in drug discovery campaigns according to Lipinski's Rule of 5 due to its advantageous combination of lipophilicity and hydrogen bonding ability, thereby improving the ADME properties. However, despite the high prevalence and importance of vicinal hydrogen bond donors in pharmaceutical agents, a general synthetic method for doubly difluoromethylated compounds in the vicinal position is absent. Here we describe a copper-electrocatalyzed strategy that enables the vicinal bis(difluoromethylation) of alkenes. By leveraging electrochemistry to oxidize Zn(CF2H)2(DMPU)2-a conventionally utilized anionic transmetalating source, we paved a way to utilize it as a CF2H radical source to deliver the CF2H group in the terminal position of alkenes. Mechanistic studies revealed that the interception of the resultant secondary radical by a copper catalyst and subsequent reductive elimination is facilitated by invoking the Cu(III) intermediate, enabling the second installation of the CF2H group in the internal position. The utility of this electrocatalytic 1,2-bis(difluoromethylation) strategy has been highlighted through the late-stage bioisosteric replacement of pharmaceutical agents such as sotalol and dipivefrine.
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Various contaminants of emerging concern (CECs) including pharmaceuticals and personal care products (PPCPs) have been known to threaten the aquatic ecosystem and human health even at low levels in surface water. Among them, the wide variety use of parabens as preservatives may pose potential threat to human because parabens may present estrogenic activity. Various advanced oxidation processes have been attempted to reduce parabens, but challenges using cold plasma (CP) are very rare. CP is worth paying attention to in reducing parabens because it has the advantage of generating radical ions, including reactive oxygen/nitrogen species and various ions. Accordingly, this study demonstrates how CP can be utilized and how CP competes with other advanced oxidation processes in energy requirements. Quantified ethyl-, propyl-, and butyl-paraben indicate that CP can effectively degrade them up to 99.1% within 3 h. Regression reveals that the kinetic coefficients of degradation can be increased to as high as 0.0328 min-1, comparable to other advanced oxidation processes. Many by-products generated from the oxidation of parabens provide evidence of the potential degradation pathway through CP treatment. In addition, we found that the electrical energy consumption per order of CP (39-95 kWh/m3/order) is superior to other advanced oxidation processes (69â¼31,716 kWh/m3/order). Overall, these results suggest that CP may be a viable option to prevent adverse health-related consequences associated with parabens in receiving water.
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Oxirredução , Parabenos , Poluentes Químicos da Água , Parabenos/química , Poluentes Químicos da Água/química , Gases em Plasma/química , Cinética , Conservantes Farmacêuticos/químicaRESUMO
Posterior reversible encephalopathy syndrome (PRES) is a rare neurological disease that may be associated with hypertension, autoregulatory failure, and the use of calcineurin inhibitors following heart transplantation (HT). In this article, we present a case series of PRES, discussing its potential causes and management strategies. Among the 126 HT recipients at our hospital, four were diagnosed with PRES. Three of these patients developed PRES within 7 days after HT. Prior to the onset of PRES, all patients experienced sustained hypertension, and strict blood pressure (BP) control was maintained. Three of the four patients recovered without PRES recurrence, while one patient died of sepsis after an episode of altered consciousness. Hypertension was observed in all patients prior to the onset of PRES, and the majority experienced symptom improvement with BP control. While most cases of PRES were reversible with conservative treatment, including the administration of antiepileptics, one irreversible case resulted in in-hospital mortality. Thus, PRES can have serious outcomes and is not invariably benign.
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Tetramethylammonium hydroxide (TMAH), which is a chemical used in the electronic industry, is classified as a hazardous material (HAZMAT class 8) that threatens aquatic ecosystems and human health. Consequently, numerous studies have attempted to remove TMAH using various treatment methods, including advanced oxidation processes such as ozone, UV, or Fenton oxidation. However, prior research has indicated a low kinetic rate of TMAH removal. In this context, we proposed an alternative to TMAH degradation by combining a cold plasma (CP) process with periodate oxidation. As for the kinetics of TMAH removal, the kinetic constant was improved by 5 times (0.1661 and 0.0301 for 40.56 and 2.2 W, respectively) as the electric power of a CP system increased from 2.2 to 40.56 W. The kinetic constant of a 40.56 W CP system further increased by 54 times (1.6250) than a 2 W CP system when 4 mM periodate was used simultaneously. As a result, the integrated CP/periodate system represented 2 times higher TMAH removal efficiency (29.5%) than a 2 W CP system (14.4%). This excellent TMAH degradation capability of the integrated CP/periodate system became pronounced at pH 10 and 25 °C. Overall, the integrated CP/periodate system is expected to be a viable management option for effectively controlling hazardous TMAH chemicals.
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Oxirredução , Compostos de Amônio Quaternário , Poluentes Químicos da Água , Cinética , Compostos de Amônio Quaternário/química , Ácido Periódico/química , Gases em Plasma , AnimaisRESUMO
Understanding the distribution of hundreds of thousands of plant metabolites across the plant kingdom presents a challenge. To address this, we curated publicly available LC-MS/MS data from 19,075 plant extracts and developed the plantMASST reference database encompassing 246 botanical families, 1,469 genera, and 2,793 species. This taxonomically focused database facilitates the exploration of plant-derived molecules using tandem mass spectrometry (MS/MS) spectra. This tool will aid in drug discovery, biosynthesis, (chemo)taxonomy, and the evolutionary ecology of herbivore interactions.
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The endangered and poorly known Swamp Grass-babbler, Laticilla cinerascens (Passeriformes: Pellorneidae), confronts critical threats and vulnerability due to its specific habitat requirements and restricted populations in the northeastern region of the Indian Subcontinent. This study investigates the distribution of the species, habitat quality, geometry and shape complexity of connectivity among the protected areas (PAs), and responses to climate change in Northeast India under different climate change pathways by utilizing ensemble distribution models, and ecological metrics. From the total distribution extent (1,42,000 km2), approximately 9366 km2 (6.59 %) is identified as the suitable habitat for this threatened species. Historically centered around Dibru Saikhowa National Park (DSNP), the species faced a drastic decline due to anthropogenic activities and alteration in land use and lover cover. The study also reveals a significant decline in suitable habitat for L. cinerascens in future climate scenarios, with alarming reductions under SSP126 (>10 % in the timeframe 2041-2060 and > 30 % from 2061 to 2080), SSP245 (>90 % in both time periods), and SSP585 (>90 % in both timeframes) from the present scenario. At present, DSNP has the most suitable habitat within the distribution range but is projected to decline (>90 %) under more severe climate change scenarios, as observed in other PAs. Landscape fragmentation analysis indicates a shift in habitat geometry, highlighting the intricate impact of climate change. It predicts a substantial 343 % increase (in the SSP126) in small habitat patches in the future. Connectivity analysis among PAs shows a significant shift, with a decline exceeding 20 %. The analysis of shape complexity and connectivity geometry reveals a significant increase of over 220 % in the fragmentation of connectivity among PAs between 2061 and 2080 under the SSP585 climate change scenario compared to the present conditions. The study underscores the urgent need for conservation actions, emphasizing the complex interplay of climate change, habitat suitability, and fragmentation. Prioritizing PAs with suitable habitats and assessing their connectivity is crucial. Adaptive management strategies are essential to address ongoing environmental changes and safeguard biodiversity. Future research in critical areas is needed to establish long-term monitoring programs to lead/extend effective conservation strategies.
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OBJECTIVE: To determine if insomnia-related factors differ depending on the presence of depression in patients with epilepsy. METHODS: This cross-sectional multicenter study collected data on depressive symptoms, insomnia symptoms, and excessive daytime sleepiness, which were defined as a Patient Health Questionnaire-9 (PHQ-9) score of ≥ 10, an Insomnia Severity Index (ISI) score of ≥ 15, and an Epworth Sleepiness Scale (ESS) of ≥ 11, respectively. Further, uncontrolled seizures were defined as one or more seizures per month during antiseizure medications treatment. A stepwise logistic regression analysis was conducted, with a logistic regression with interaction terms performed to identify differences in insomnia-related factors depending on depressive symptoms. RESULTS: Of 282 adults with epilepsy (men, 58 %; mean age, 40.4 ± 13.9 years), a PHQ-9 score ≥ 10, an ISI score ≥ 15, an ESS score ≥ 11 were noted in 23.4 % (n = 66), 20.2 % (n = 57), and 12.8 % (n = 36), respectively. More patients with depressive symptoms had an ISI score ≥ 15 (56.1 % vs. 9.3 %; p < 0.001) than those without. In multiple logistic regression, uncontrolled seizures (odds ratio [OR], 4.896; p < 0.01), daytime sleepiness (OR, 5.369; p < 0.05), and a history of psychiatric disorders (OR, 3.971; p < 0.05) were identified as significant factors that were more likely to be associated with an ISI score ≥ 15; however, this was only true in patients without depressive symptoms. In contrast, use of perampanel (OR, 0.282; p < 0.05) was less likely associated, while female sex (OR, 3.178; p < 0.05) was more likely associated with an ISI score ≥ 15 only in patients with depressive symptoms. CONCLUSIONS: Insomnia-related factors in patients with epilepsy may differ between patients with and without depression. Our findings of different insomnia-related factors based on the presence of depression may facilitate the management of patients with epilepsy.
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Depressão , Epilepsia , Distúrbios do Início e da Manutenção do Sono , Humanos , Masculino , Feminino , Distúrbios do Início e da Manutenção do Sono/complicações , Distúrbios do Início e da Manutenção do Sono/psicologia , Adulto , Epilepsia/complicações , Epilepsia/psicologia , Estudos Transversais , Pessoa de Meia-Idade , Depressão/epidemiologia , Depressão/complicações , Adulto Jovem , Modelos Logísticos , Anticonvulsivantes/uso terapêutico , Inquéritos e Questionários , Índice de Gravidade de DoençaRESUMO
Research to increase biomethane recovery efficiency from thickened sewage sludge (TSWS) using sustainable anaerobic digestion (AD) in municipal wastewater treatment plants is ongoing. Pretreating substrates is known to increase organic biodegradation and biomethane conversion rates in AD. Cold plasma (CP), a recently adopted advanced oxidation processes (AOP) has emerged as an alternative to accelerate pretreatment times under different operation variables. This study assessed raw and CP-pretreated TSWS in an anaerobic sequencing batch reactor (ASBR) and anaerobic membrane bioreactor (AnMBR). The effects of incremental organic loading rates (OLR) and nitrogenous compounds concentration on enhanced CH4 bioconversion efficiency were evaluated. We found that the AnMBR outperformed the ASBR, with an overall chemical oxygen demand (COD) conversion rate of 67%, lower total nitrogen (T-N) accumulation (594 mg L-1), and an overall methane yield of 0.24 L CH4 g-1 COD. CP pretreatment improved TSWS AD, resulting in more efficient COD removal and methane recovery. This study suggests that CP technology is a promising pretreatment to improve AD when treating TSWS.
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Biodegradação Ambiental , Reatores Biológicos , Metano , Nitrogênio , Gases em Plasma , Esgotos , Eliminação de Resíduos Líquidos , Metano/metabolismo , Anaerobiose , Nitrogênio/metabolismo , Esgotos/química , Hidrólise , Eliminação de Resíduos Líquidos/métodos , Análise da Demanda Biológica de Oxigênio , Águas Residuárias/químicaRESUMO
Conventional pretreatment technologies have been assessed to resolve the slow hydrolysis of sewage sludge, but high operating costs have prevented their wide use. This study investigated non-thermal plasma (NTP) technologies as an alternative to promote anaerobic digestion (AD). Various contact time (CT) and temperature (T) conditions were used to assess how NTP pretreatment improves the methane conversion of organics in sewage sludge. A multi-response surface model (RSM) using a central composite design (CCD) identified the optimal CT (4.6 h) and T (45 °C). This statistical optimization of NTP pretreatment led to an enhanced biochemical methane potential of 297 ± 46 mL CH4 g-1 COD by reducing operating cost as power consumption as low as 0.08 USD L-1. The result was comparable to those of other advanced oxidation processes (0.14 - 0.60 USD L-1) demonstrating that accelerated hydrolysis of sewage sludge using NTP pretreatment show potential for improving renewable energy recovery from sewage sludge.
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Metano , Esgotos , Esgotos/química , Hidrólise , Eliminação de Resíduos Líquidos/métodos , Gases em Plasma , AnaerobioseRESUMO
STUDY DESIGN: Retrospective study. OBJECTIVE: This study compared the fusion and subsidence rate and clinical outcomes when using different-sized static PEEK cages in BE-TLIF. SUMMARY OF BACKGROUND DATA: Biportal endoscopic techniques for transforaminal lumbar interbody fusion (BE-TLIF) have been shown to have similar clinical and fusion outcomes with faster clinical recovery in comparison to tubular surgery. Subsidence of the interbody, however, could be a complication. METHODS: Patients who underwent 1 or 2 level BE-TLIF for degenerative and isthmic spondylolisthesis between January 2019 and January 2022 were included. A 32×10 mm cage (group A) and a 40×15 mm cage (group B) were compared. The visual analog scale (VAS) for back and leg symptoms, and Oswestry disability index (ODI) were collected. Plain radiographs and computed tomography assessed fusion and subsidence at a minimum of 12 months. RESULTS: Of the 69 enrolled patients, 39 group A patients (51 levels) and 30 group B patients (32 levels) were compared. The operation time per level was 123 ± 15.8 and 138 ± 10.5 minutes per fusion level in groups A and B, respectively (P < 0.05). ODI improved from 64.8 ± 6.2 to 15.7 ± 7.1 in group A and from 65.3 ± 5.6 to 15.1 ± 6.3 in group B at the final follow-up (P < 0.05). VAS leg and back score improvement between the groups did not differ; however, the 3-month postoperative VAS back improvement was significantly higher in group B. The final fusion rate at the final follow-up did not significantly differ; however, the fusion ratio at 1 year was higher in group B (P < 0.05). Subsidence occurred in 5 cases (9.8%) in group A and none in group B (P < 0.05). CONCLUSION: BE-TLIF using a larger cage can be performed safely with similar patient-reported outcome measures with a faster fusion rate with less subsidence risk. LEVEL OF STUDY: III.
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Background: Researchers have attempted to understand the underlying mechanism of the Latarjet procedure; however, its effects on shoulder kinematics have not been well studied. Purpose/Hypothesis: The purpose was to analyze shoulder kinematics after the Latarjet procedure. It was hypothesized that the nonanatomic transfer of the coracoid process during the procedure would affect normal shoulder kinematics. Study Design: Controlled laboratory study. Methods: The study included 10 patients (age range, 20-52 years) who underwent the modified Latarjet procedure between June 2016 and November 2021. Computed tomography and fluoroscopy were conducted on both shoulder joints of all patients, and 3-dimensional models were reconstructed. The 3-dimensional coordinates were encoded on the reconstructed models, and shoulder kinematics were analyzed through a 3-dimensional-2-dimensional model-image registration technique. Scapular rotation parameters (scapular upward rotation, posterior tilt, external rotation, and scapulohumeral rhythm) were compared between the Latarjet and the nonsurgical contralateral sides during humeral abduction, as was anteroposterior (AP) translation relative to the glenoid center during active humeral external rotation. Results: The Latarjet side displayed significantly higher values of scapular upward rotation at higher degrees of humeral elevation (130°, 140°, and 150°) compared with the nonsurgical side (P = .027). Posterior tilt, external rotation, and scapulohumeral rhythm were not significantly different between sides. AP translation at maximal humeral rotation was not significantly different between sides (Latarjet, -0.06 ± 5.73 mm vs nonsurgical, 5.33 ± 1.60 mm; P = .28). Interestingly, on the Latarjet side, AP translation increased until 40° of humeral rotation (4.27 ± 4.64 mm) but began to decrease from 50° of humeral rotation. Conclusion: The Latarjet side demonstrated significant changes in scapular upward rotation during higher degrees of humeral elevation compared with the contralateral shoulder. Posterior movement of the humeral head at >50° of humeral rotation could be the desired effect of anterior stabilization; however, researchers should evaluate long-term complications such as osteoarthritis. Clinical Relevance: Analysis of shoulder kinematics after the Latarjet procedure could provide information regarding long-term outcomes and whether the procedure would affect the daily activities of patients.
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Glycerol dehydrogenase (GDH) catalyzes glycerol oxidation to dihydroxyacetone in a NAD+-dependent manner. As an initiator of the oxidative pathway of glycerol metabolism, a variety of functional and structural studies of GDH have been conducted previously. Structural studies revealed intriguing features of GDH, like the flexible ß-hairpin and its significance. Another commonly reported structural feature is the enzyme's octameric oligomerization, though its structural details and functional significance remained unclear. Here, with a newly reported GDH structure, complexed with both NAD+ and glycerol, we analyzed the octamerization of GDH. Structural analyses revealed that octamerization reduces the structural dynamics of the N-domain, which contributes to more consistently maintaining a distance required for catalysis between the cofactor and substrate. This suggests that octamerization may play a key role in increasing the likelihood of the enzyme reaction by maintaining the ligands in an appropriate configuration for catalysis. These findings expand our understanding of the structure of GDH and its relation to the enzyme's activity.
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NAD , Desidrogenase do Álcool de Açúcar , NAD/metabolismo , Glicerol/metabolismo , Desidrogenase do Álcool de Açúcar/metabolismo , Oxirredução , Glutamato Desidrogenase/metabolismoRESUMO
The hispid hare, Caprolagus hispidus, belonging to the family Leporidae is a small grassland mammal found in the southern foothills of the Himalayas, in India, Nepal, and Bhutan. Despite having an endangered status according to the IUCN Red List, it lacks studies on its distribution and is threatened by habitat loss and land cover changes. Thus, the present study attempted to assess the habitat suitability using the species distribution model approach for the first time and projected its future in response to climate change, habitat, and urbanization factors. The results revealed that out of the total geographical extent of 188,316 km2, only 11,374 km2 (6.03%) were identified as suitable habitat for this species. The results also revealed that habitat significantly declined across its range (>60%) under certain climate change scenarios. Moreover, in the present climate scenario protected areas such as Shuklaphanta National Park (0.837) in Nepal exhibited the highest mean extent of habitat whereas, in India, Dibru-Saikhowa National Park (0.631) is found to be the most suitable habitat. Notably, two protected areas in Uttarakhand, India, specifically Corbett National Park (0.530) and Sonanandi Wildlife Sanctuary (0.423), have also demonstrated suitable habitats for C. hispidus. Given that protected areas showing a future rise in habitat suitability might also be regarded as potential sites for species translocation, this study underscores the importance of implementing proactive conservation strategies to mitigate the adverse impacts of climate change on this species. It is essential to prioritize habitat restoration, focused protection measures, and further species-level ecological exploration to address these challenges effectively. Furthermore, fostering transboundary collaboration and coordinated conservation actions between nations is crucial to safeguarding the long-term survival of the species throughout its distribution range.
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In this paper, we propose a method for the three-dimensional (3D) image visualization of objects under photon-starved conditions using multiple observations and statistical estimation. To visualize 3D objects under these conditions, photon counting integral imaging was used, which can extract photons from 3D objects using the Poisson random process. However, this process may not reconstruct 3D images under severely photon-starved conditions due to a lack of photons. Therefore, to solve this problem, in this paper, we propose N-observation photon-counting integral imaging with statistical estimation. Since photons are extracted randomly using the Poisson distribution, increasing the samples of photons can improve the accuracy of photon extraction. In addition, by using a statistical estimation method, such as maximum likelihood estimation, 3D images can be reconstructed. To prove our proposed method, we implemented the optical experiment and calculated its performance metrics, which included the peak signal-to-noise ratio (PSNR), structural similarity (SSIM), peak-to-correlation energy (PCE), and the peak sidelobe ratio (PSR).
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Digital Holographic Microscopy (DHM) is a 3D imaging technology widely applied in biology, microelectronics, and medical research. However, the noise generated during the 3D imaging process can affect the accuracy of medical diagnoses. To solve this problem, we proposed several frequency domain filtering algorithms. However, the filtering algorithms we proposed have a limitation in that they can only be applied when the distance between the direct current (DC) spectrum and sidebands are sufficiently far. To address these limitations, among the proposed filtering algorithms, the HiVA algorithm and deep learning algorithm, which effectively filter by distinguishing between noise and detailed information of the object, are used to enable filtering regardless of the distance between the DC spectrum and sidebands. In this paper, a combination of deep learning technology and traditional image processing methods is proposed, aiming to reduce noise in 3D profile imaging using the Improved Denoising Diffusion Probabilistic Models (IDDPM) algorithm.