High Probability Research Articles

Utilization of machine learning methods for prediction of acute and late rectal toxicity due to curative prostate radiotherapy.

Rectal toxicity is one of the primary dose-limiting side effects of prostate cancer radiotherapy, and consequential impairment on quality of life in these patients with long survival is an important problem. In this study, we aimed to evaluate the possibility of predicting rectal toxicity with artificial intelligence model which was including certain dosimetric parameters. One hundred and thirty-seven patients with a diagnosis of prostate cancer who received curative radiotherapy for prostate +/- pelvic lymphatics were included in the study. The association of the clinical data and dosimetric data between early and late rectal toxicity reported during follow-up was evaluated. The sample size was increased to 274 patients by synthetic data generation method. To determine suitable models, 15 models were studied with machine learning algorithms using Python 2.3, Pycaret library. Random forest classifier was used with to detect active variables. The area under the curve and accuracy were found to be 0.89-0.97 and 95%-99%, respectively, with machine learning algorithms. The sensitivity values for acute and toxicity were found to be 0.95 and 0.99, respectively. Early or late rectal toxicity can be predicted with a high probability via dosimetric and physical data and machine learning algorithms of patients who underwent prostate +/- pelvic radiotherapy. The fact that rectal toxicity can be predicted before treatment, which may result in limiting the dose and duration of treatment, makes us think that artificial intelligence can enter our daily practice in a short time in this sense.

Neurons of Macaque Frontal Eye Field Signal Reward-Related Surprise.

The frontal eye field (FEF) plays a well-established role in the control of visual attention. The strength of an FEF neuron's response to a visual stimulus presented in its receptive field is enhanced if the stimulus captures spatial attention by virtue of its salience. A stimulus can be rendered salient by cognitive factors as well as by physical attributes. These include surprise. The aim of the present experiment was to determine whether surprise-induced salience would result in enhanced visual response strength in the FEF. Toward this end, we monitored neuronal activity in two male monkeys while presenting first a visual cue predicting with high probability that the reward delivered at the end of the trial would be good or bad (large or small) and then a visual cue announcing the size of the impending reward with certainty. The second cue usually confirmed but occasionally violated the expectation set up by the first cue. Neurons responded more strongly to the second cue when it violated than when it confirmed expectation. The increase in firing rate was accompanied by a decrease in spike-count correlation as expected from capture of attention. Although both good surprise and bad surprise induced enhanced firing, the effects appeared to arise from distinct mechanisms as indicated by the fact that the bad-surprise signal appeared at a longer latency than the good-surprise signal, and by the fact that the strength of the two signals varied independently across neurons.Significance Statement Neurons in the macaque frontal eye field (FEF) respond strongly to cues predicting rewards. Their firing might be related to the representation of value or to the capture of attention. We set out to resolve this issue by monitoring neuronal responses to cues conveying surprising information about upcoming rewards. We find that surprising cues elicit enhanced responses regardless of whether the surprise is good (more reward than expected) or bad (less reward than expected). These findings, which constitute the first evidence for surprise-driven activity in the FEF, are most harmonious with an interpretation based on capture of attention.

The Pivotal Role of Presepsin in Assessing Sepsis-Induced Cholestasis

Background: The serum levels of presepsin correlate with parameters indicating cholestasis in sepsis; however, the probability and significance of this association remain uncertain. We aimed to ascertain whether infection, as signaled by presepsin levels, is the primary determinant of elevated biliary parameters in sepsis. Methods: A unicenter, retrospective study included 396 COVID-free emergency-admitted patients, in which presepsin level was determined. Presepsin, neutrophil count, leukocyte count, C reactive protein, and fibrinogen evaluated the septic/inflammatory state. The statistically significant factors associated with cholestasis, ALT, and AST were analyzed by Fisher’s exact test and Spearman regression with Bonferroni’s correction. Results: Presepsin emerged as the most likely variable correlated with all cholestasis markers: alkaline phosphatase (p = 7 × 10−8), gamma-glutamyl transferase (p = 5 × 10−10), and conjugated bilirubin (p = 4 × 10−15). Thrombocyte count, C reactive protein, age, creatinine, urea, lactate, and blood pressure, were associated with only one or two of these markers. Conclusions: In a sepsis setting, the increase in cholestasis-related parameters is associated with presepsin with a higher probability than hemodynamic, inflammatory, or coagulation-related variables. Determining this robust link between sepsis and cholestasis could eliminate unnecessary imaging procedures in critically ill patients, enabling clinicians to focus efforts on addressing the primary infectious cause.

The Inhibitory Effects of Maclurin on Fatty Acid Synthase and Adipocyte Differentiation

Obesity is a complex health condition characterized by excessive adipose tissue accumulation, leading to significant metabolic disturbances such as insulin resistance and cardiovascular diseases. Fatty acid synthase (FAS), a key enzyme in lipogenesis, has been identified as a potential therapeutic target for obesity due to its role in adipocyte differentiation and lipid accumulation. This study employed a multidisciplinary approach involving in silico and in vitro analyses to investigate the anti-adipogenic properties of maclurin, a natural phenolic compound derived from Morus alba. Using SwissDock software (ChEMBL version 23), we predicted protein interactions and demonstrated a high probability (95.6%) of maclurin targeting FAS, surpassing the interaction rates of established inhibitors like cerulenin. Docking simulations revealed maclurin’s superior binding affinity to FAS, with a binding score of −7.3 kcal/mol compared to −6.7 kcal/mol for cerulenin. Subsequent in vitro assays confirmed these findings, with maclurin effectively inhibiting FAS activity in a concentration-dependent manner in 3T3-L1 adipocytes, without compromising cell viability. Furthermore, maclurin treatment resulted in significant reductions in lipid accumulation and the downregulated expression of critical adipogenic genes such as PPARγ, C/EBPα, and FAS, indicating the suppression of adipocyte differentiation. Maclurin shows potential as a novel FAS inhibitor with significant anti-adipogenic effects, offering a promising therapeutic avenue for the treatment and prevention of obesity.

Evaluation by app in smartphones of awake bruxism at the return of presential classes in two university centers

Background. The return to normality post-pandemic brought some inconveniences to the population, especially students. To evaluate the frequency of awake bruxism behaviors through the use of an app on smartphones in dental students returning to presential classes. Awake bruxism was evaluated with the creation of an app that according to the authors evaluates: relaxed jaw muscles, dental contact, jaw effort, clenching teeth and teeth grinding, 5 frequent oral conditions in the population. The frequency of awake/daytime bruxism (AB) in healthy individuals when comparing other populations with possible risk factors for additive bruxism (psychological factors, depression, suicide delusions, etc.), evaluating consequent clinical signs (fatigue, muscle pain, attritions and dental openings). Methods: The sample of three hundred (n=300) young adults legally enrolled in two Ecuadorian universities, the sample was selected among fifth, sixth, seventh, eighth and ninth semester students legally enrolled and who are attending Faculty of Dentistry classes in 2 different cities (Quito and Guayaquil). The app was configured to provide 20 alerts during the day x seven days a week, in real time. Results. The study obtained 95% reliability and 5% error in research, was used. The relaxation condition was present in all users, but 40% of the alerts were associated with jaw and tooth discomfort, 39% corresponded to the discomfort of mandibular clenching, and 24% corresponded to tooth contact. A direct significant association was found between the state of relaxation and nonrelaxation, with a high probability of reports related to nonrelaxation (p ≤ 0.05). Conclusions: Awake bruxism with the app was evaluated, identifying 5 behaviors such as: relaxed mandibular muscles, dental contact, mandibular effort, clenching and grinding teeth, frequent conditions in the population; reporting a state of mandibular relaxation, there is a high probability that a condition of nonrelaxation would be reported (p≤0.05).

Efficacy of Photodynamic Therapy in the Treatment of Actinic Keratosis: A Network Meta-Analysis.

Photodynamic therapy (PDT) is an effective treatment for actinic keratosis (AK) and uses different light sources as well as photosensitizers. In addition, PDT is often combined with other physical therapies or drugs. This study was aimed to compare the efficacy of different PDTs against AK lesions based on Complete Response (CR) by conducting a network meta-analysis (NMA). Randomized controlled trials (RCTs) using PDT for AK were screened and a Bayesian model was developed to perform an NMA of CR at 3 months after the first treatment. Twenty-six trials involving 2285 patients and 14 treatments were included. The treatments were broadly divided into mono-PDT and combination therapy. The photodynamic monotherapies included methyl 5-aminolevulinic acid (MAL)-daylight (DL)-PDT, MAL-light-emitting diode (LED)-PDT, 5-aminolevulinic acid (ALA)-LED-PDT, etc. Combination therapies included ablative fractional laser (AFL)-assisted MAL-LED-PDT, calcipotriol (CAL)-assisted MAL-LED-PDT, and 5-fluorouracil (5-Fu)-assisted MAL-DL-PDT. The results of the NMA showed that there is a high probability that AFL-MAL-LED-PDT is the most effective treatment option, followed by CAL-MAL-LED-PDT and ALA-LED-PDT. The subgroup analysis showed that MAL-based PDT had better efficacy when using LED versus other light sources, while LED-based PDT was likely to have better efficacy when using ALA versus other photosensitizers. The results of this NMA suggest that AFL-MAL-LED-PDT may be the superior choice for achieving complete clearance of AK lesions. PDT using LED as the light source and ALA as the photosensitizer may be more effective for the treatment of AK. However, more RCTs are needed to verify the results of this analysis.

Mechanochemical Diversity in Block Copolymers.

Covalent polymer chains are known to undergo mechanochemical events when subjected to mechanical forces. Such force-coupled reactions, like C-C bond scission in homopolymers, typically occur in a non-selective manner but with a higher probability at the mid-chain. In contrast, block copolymers (BCPs), composed of two or more chemically distinct chains linked by covalent bonds, have recently been shown to exhibit significantly different mechanochemical reactivities and selectivities. These differences may be attributable to the atypical conformations adopted by their chains, compared to the regular random coil. Beyond individual molecules, when BCPs self-assemble into ordered aggregates in solution, the non-covalent interactions between the chains lead to meaningful acceleration in the activation of embedded force-sensitive motifs. Furthermore, the microphase segregation of BCPs in bulk creates periodically dispersed polydomains, locking the blocks in specific conformations which have also been shown to affect their mechanochemical reactivity, with different morphologies influencing reactivity to varying extents. This review summarizes the studies of mechanochemistry in BCPs over the past two decades, from the molecular level to assemblies, and up to bulk materials.

Test of the minimum supero-inferior femoral neck diameter as a sex predictor in a contemporary documented osteological collection from Portugal

Abstract Adult sex estimation is one of the first and most important steps in forensic examination. While dealing with disturbed burials, the most dimorphic anatomic areas of the skeleton (such as the coxae, the skull and the head of femur and humerus) may be deteriorated or fragmented. In contrast, the minimum supero-inferior femoral neck diameter (SID) is generally much better preserved. The aim of the present research is to identify the discriminatory potential of SID for sex estimation and to test different formulae and mathematical procedures currently available in the forensic literature, on a sample of 295 contemporary individuals from the 21st Century Identified Skeletal Collection (University of Coimbra, Portugal), in order to identify its relevance for application in Portuguese forensic cases. Results showed that SID is a dimorphic variable, with high frequencies and probabilities of cases correctly estimated (0.82 and 0.83, respectively); statistically significant differences between females and males, and a high association between the metrics and sex, were identified. Posterior probabilities allow reliable estimations for all the measurements, excepting those between 31.0 and 31.5 mm, and the procedures that show the highest accuracy are those proposed by Seidemann et al. (1998), Curate et al. (2016) and Luna et al. (2021), with frequencies and probabilities between 0.82 and 0.83 for both sexes. The validation procedures implemented in this study highlight both the need to test quantitative models generated from diverse contemporary human populations, and the value of SID for obtaining reliable adult sex estimates, as they improve the quality of the biological profiles obtained in forensic contexts. Key points

Bayesian reverse design of high-efficiency perovskite solar cells based on experimental knowledge constraints

To alleviate high costs and lengthy trial-and-error periods associated with traditional optimization methods for perovskite solar cells (PSCs), we developed a data-driven reverse design framework for high-efficiency PSCs. This framework integrates machine learning and Bayesian optimization (BO) to accelerate the optimization process of PSCs by intelligently recommending the most promising parameter configurations for PSCs, such as device structure and fabrication processes. To improve the robustness of the framework, we first designed a two-stage sampling strategy to alleviate the issue of imbalanced dataset classes. Subsequently, by integrating “experimental knowledge constraints” into the BO process, we achieved precise parameter configurations, thus avoiding discrepancies between predicted and actual results due to parameter mismatches. Finally, using SHapley Additive exPlanations, we unveiled key factors influencing the power conversion efficiency (PCE), such as the composition of perovskite solvents. Our framework not only precisely predicted the PCE of PSCs with an area under the curve of 0.861 but also identified the optimal parameter configurations, achieving a high probability of 0.981. This framework offers substantial support for minimizing redundant experiments and characterizations, effectively accelerating the optimization process of PSCs.

Cardiac Arrest during Temporary Clipping for Ruptured Internal Carotid Artery Aneurysm: A Case Report

Abstract Objectives Mechanical stimulation of the trigeminal nerve during craniofacial, skull base, or dental surgeries may cause bradycardia, hypotension, or cardiac arrest. This phenomenon is called trigeminal cardiac reflex (TCR). We encountered a rare case of a patient who experienced sinus arrest due to temporary clipping of the intracranial carotid artery during the clipping of a ruptured aneurysm. We discuss possible reasons for the occurrence of TCR in this case. Materials and Methods A man in his 30s with no medical history presented with a sudden-onset headache. Computed tomography revealed a subarachnoid hemorrhage in the basal cistern and left Sylvian fissure. Angiography revealed a saccular aneurysm of the left internal carotid-anterior choroidal artery. A left frontotemporal craniotomy and dural incision were performed, followed by a trans-Sylvian approach. Cardiac arrest occurred twice during the temporary clipping of the intracranial carotid artery. After surgery, we performed a cardiac ultrasound echo and a 1-week Holter electrocardiogram. Neither showed abnormalities. No arrhythmia or cardiac events were observed over a one and half-year follow-up period. Results The cardiac arrest might have been triggered by the stimulation of the trigeminal nerve in the internal carotid artery. The repeated and anatomical features of this case suggest that TCR triggered cardiac arrest. Conclusion The high probability that cardiac arrest was induced by trigeminal nerve stimulation should be considered during the temporary clipping of the internal carotid artery. However, the predisposing factors and exact underlying mechanisms for these arrhythmias remain unknown and require further investigation.

Microbial Forensics: Comparison of MLVA Results According to NGS Methods, and Forensic DNA Analysis Using MLVA

Microbial forensics is a scientific discipline for analyzing evidence related to biological crimes by identifying the origin of microorganisms. Multiple locus variable number tandem repeat analysis(MLVA) is one of the microbiological analysis methods used to specify subtypes within a species based on the number of tandem repeat in the genome, and advances in next generation sequencing(NGS) technology have enabled <i>in silico</i> anlysis of full-length whole genome sequences. In this paper, we analyzed unknown samples provided by Robert Koch Institute(RKI) through The United Nations Secretary-General’s Mechanism(UNSGM)’s external quality assessment exercise(EQAE) project, which we officially participated in 2023. We confirmed that the 3 unknown samples were <i>B. anthracis</i> through nucleic acid isolation and genetic sequence analysis studies. MLVA results on 32 loci of <i>B. anthracis</i> were analysed by using genome sequences obtained from NGS(NextSeq and MinION) and Sanger sequencing. The MLVA typing using short-reads based NGS platform(NextSeq) showed a high probability of causing assembly error when a size of the tandem repeats was grater than 200 bp, while long-reads based NGS platform(MinION) showed higher accuracy than NextSeq, although insertion and deletion was observed. We also showed hybrid assembly can correct most indel error caused by MinION. Based on the MLVA results, genetic identification was performed compared to the 2,975 published MLVA databases of <i>B. anthracis</i>, and MLVA results of 10 strains were identical with 3 unkonwn samples. As a result of whole genome alignment of the 10 strains and 3 unknown samples, all samples were identified as <i>B. anthracis</i> strain A4564 which is associated with injectional anthrax isolates in heroin users.

Reducing Multiphoton Noise in Multiplexed Single-Photon Sources

Multiplexed single-photon sources can produce indistinguishable single photons with high probability in near-perfect spatial modes. Such systems, realized with optical elements having losses, can be optimized—that is, both the optimal number of multiplexed units in the sources and the optimal mean number of photon pairs generated in a multiplexed unit, for which the output single-photon probability is maximal, can be determined. The accompanying multiphoton noise of the sources, arising from the probabilistic nature of the underlying physical processes in these systems, can be detrimental in certain applications. Inspired by this fact, we develop a procedure aimed at decreasing the multiphoton noise of multiplexed single-photon sources. The procedure is based on the reoptimization of the system for the chosen value of the normalized second-order autocorrelation function characterizing the multiphoton noise. The results of this reoptimization are shown for two types of spatially multiplexed single-photon sources. We find that by applying the proposed procedure, the multiphoton noise can be considerably decreased along with a relatively low decrease in the single-photon probability. Although the method presented here is for two spatially multiplexed single-photon sources, it can be applied straightforwardly for any type of multiplexed single-photon source.

Determinants of possible inflammatory myocardial damage in acute intestinal infections in children

BACKGROUND: Non-coronary cardiomyopathies, including inflammatory cardiomyopathies, are one of the leading causes of disability and mortality in children and adults. Inflammatory cardiomyopathy in most cases is an outcome of myocarditis as a result of direct agent-dependent myocardial damage or autoimmune reactions in the absence of genetic predisposition. AIM: On the basis of clinical assessment of cardiovascular system changes, to develop a discriminant model to predict the possibility of myocardial damage of inflammatory genesis in acute intestinal infections (AII) in children. MATERIALS AND METHODS: In the Intestinal Infections Department of the Children’s Research and Clinical Center for Infectious Diseases of FMBA of Russia in the period 2020-2022, 33 children aged from 1 month to 13 years with AII of different etiology were consecutively observed, in whom, according to clinical, laboratory and instrumental examination data, for the first time in their lives, changes in cardiovascular system were detected. The sample was formed using an algorithm for diagnosing inflammatory myocardial lesions in points, the sum of which concluded that there were no or presence of such, which allowed us to identify group 1 (n = 24) and group 2 (n = 9), respectively. Etiological diagnosis of acute intestinal infections was performed in all children, clinical and laboratory data, results of a 12-channel electrocardiogram (ECG), transthoracic echocardiography (EchoCG) were evaluated. The differences in the groups were revealed using the Pearson chi-squared test and the Mann–Whitney test, which were considered reliable at p 0.05. The method of discriminant analysis was used. RESULTS: Functional systolic noise and increased cardiospecific enzymes were observed less frequently in group 1 than in group 2 (4.2%; 22.2% and 67%; 100%). Of the pathological ECG changes, violations of the repolarization process were observed (16.7%; 33.3%). No significant changes in the Echo-KG were detected. The viral etiology of acute intestinal infections dominated (79.2%; 88.9%). Changes in the hemogram were characterized by a high frequency of leukocytosis in group 1 (29.2%; 0%) and leukopenia in group 2 (4.2%; 22.2%). In group 1, there was a higher frequency of neutrophilosis (79.2%; 44.4%), rod-shaped shift (62.5%; 22.2%), thrombocytosis (29.2%; 0%), lymphocytopenia (95.8%; 55.6%; p 0.05), monocytosis (8.3%; 0%); increased C-reactive protein (41.7%; 33.3%), ALT (29.2%; 11.1%), urea (29.2%; 11.1%), leukocyturia (16.7%; 0%). CONCLUSIONS: Clinical evaluation of cardiovascular system changes in children with acute intestinal infections using a discriminant model allows to exclude myocardial damage of inflammatory genesis with high probability (95.7%), which is of practical importance.

Programmable silicon-photonic quantum simulator based on a linear combination of unitaries

Simulating the dynamic evolution of physical and molecular systems in a quantum computer is of fundamental interest in many applications. The implementation of dynamics simulation requires efficient quantum algorithms. The Lie-Trotter-Suzuki approximation algorithm, also known as the Trotterization, is basic in Hamiltonian dynamics simulation. A multi-product algorithm that is a linear combination of multiple Trotterizations has been proposed to improve the approximation accuracy. However, implementing such multi-product Trotterization in quantum computers remains challenging due to the requirements of highly controllable and precise quantum entangling operations with high success probability. Here, we report a programmable integrated-photonic quantum simulator based on a linear combination of unitaries, which can be tailored for implementing the linearly combined multiple Trotterizations, and on the simulator we benchmark quantum simulation of Hamiltonian dynamics. We modify the multi-product algorithm by integrating it with oblivious amplitude amplification to simultaneously reach high simulation precision and high success probability. The quantum simulator is devised and fabricated on a large-scale silicon-photonic quantum chip, which allows the initialization, manipulation, and measurement of arbitrary four-qubit states and linearly combined unitary gates. As an example, the quantum simulator is reprogrammed to emulate the dynamics of an electron spin and nuclear spin coupled system. This work promises the practical dynamics simulations of real-world physical and molecular systems in future large-scale quantum computers.

A probabilistic distributed digital twins approach for short-term stability and islanding of smart grid

The simultaneous evaluation of voltage, frequency, and transient stability enhances the reliability of the power systems, due to the transient effect of stability aspects on each other. However, different quantitative and qualitative parameters in the aspect and nonlinear structural analysis of the system make simultaneous and accurate predictions difficult. For this reason, the simultaneous probabilistic prediction of the stability state of three aspects with high certainty can be considered the most accurate method. This study presents a simultaneous prediction method for the stability aspect states by means of the decision theory and the game theory matrix on the basis of distributed digital twins (DDTs). The decision matrix weighs the aspect states in each bus using the distributed structure measurement and prioritizes the weak buses. In addition, the stability of different bus aspects is predicted using the game matrix. Furthermore, the changes in the system stability are predicted with high probability and certainty in the digital twins (DTs) graph, and if required, islanding is performed on the basis of the weak buses' priorities. The effects of the three aspects on each other, and the use of real-time data of the DDTs, have contributed to the high accuracy and speed of the proposed method. Simulations were performed on IEEE 14-bus, 39-bus, and 118-bus systems by means of MATLAB and DIgSILENT. The results show the advantages of the proposed method over other methods.

TCLNet: Turn-level contrastive learning network with reranking for dialogue state tracking

Dialogue state tracking (DST) plays a crucial role in task-oriented dialogue systems, as it interprets and tracks user intentions throughout the dialogue. The accuracy of DST directly impacts system efficiency and user experience. While existing generation-based DST models have shown promising results, effectively modeling long dialogue sequences remains a challenge. Furthermore, the greedy search decoding strategy employed by most previous works for speed is suboptimal because the probability of ground truth tokens is not always the highest. In this study, we propose a novel learning framework that addresses these issues by incorporating turn-level contrastive learning and a reranking module. Specifically, we adopt turn-level contrastive learning to progressively rectify the intermediate states of lengthy dialogues by contrasting data points at a finer granularity. Additionally, the integration of the reranking module empowers the model to make more reliable decisions at each time step by further considering alternative tokens with high probabilities. Experimental results demonstrate that our approach consistently enhances the model’s capability to handle long dialogue sequences and achieves superior performance over strong baselines on both the MultiWOZ 2.1 and MultiWOZ 2.2 datasets.

Identification of peat-fire-burnt areas among other wildfires using the peat fire index

Fires in peat soils are distinguished from other wildfires by their duration, the release of combustion pollutants dangerous to human health, carbon loss, and other environmental impacts. Peat fires can be detected by superimposing fire data extracted on the basis of the thermal anomalies of the MODIS Terra/Aqua Moderate Resolution Imaging spectroradiometer on previously developed peatland maps. It is necessary to take into account, not all forest fires in peatlands turn into underground (peat) fires. In the example of the extensive fires that occurred in Central European Russia in 2010, the potential of using fire activity indicators (fire radiative power (FRP), temperature, duration, etc., obtained according to MODIS data) to identify soil (peat) fires and separate them from surface fires was investigated. A special peat fire index (consisting of maximum values of FRP, average temperature, duration of burning, and area of ignition) was proposed and tested. A model of the peat fire index is a value that shows the degree of confidence that this fire is a peat fire. This index takes values from 0 to 1: 0 – surface fire, 1 – peat soil fire; values in the interval mean that a fire can affect both the surface and soil of the peatland. After analyzing the proportions of identified fires, we found out that the devised peat fire index is the most effective indicator compared with others. This indicator makes it possible to identify with high probability not only peat fires, but also to identify surface fires, and this reduces the area of uncertainty. Although the obtained results require verification at other sites, they provide convincing evidence that remote data can be used to detect peat fires.

High Probability of Lynch Syndrome Among Colorectal Cancer Patients Is Associated With Higher Occurrence of KRAS and PIK3CA Mutations.

In Indonesia, early-onset colorectal cancer (EOCRC) rates are higher in patients < 50 years old compared to Western populations, possibly due to a higher frequency of Lynch syndrome (LS) in CRC patients. We aimed to examine the association of KRAS and PIK3CA mutations with LS. In this retrospective cross-sectional single-center study, the PCR-HRM-based test was used for screening of microsatellite instability (MSI) mononucleotide markers (BAT25, BAT26, BCAT25, MYB, EWSR1), MLH1 promoter methylation, and oncogene mutations of BRAF (V600E), KRAS (exon 2 and 3), and PIK3CA (exon 9 and 20) in FFPE DNA samples. All the samples (n = 244) were from Dr. Sardjito General Hospital Yogyakarta, Indonesia. KRAS and PIK3CA mutations were found in 151/244 (61.88%) and 107/244 (43.85%) of samples, respectively. KRAS and PIK3CA mutations were significantly associated with MSI status in 32/42 (76.19%) and 25/42 (59.52%) of samples, respectively. KRAS mutation was significantly associated with LS status in 26/32 (81.25%) of samples. The PIK3CA mutation was present in a higher proportion in LS samples of 19/32 (59.38%), but not statistically significant. Clinicopathology showed that KRAS mutation was significantly associated with right-sided CRC and higher histology grade in 39/151 (25.83%) and 24/151 (16.44%) samples, respectively. PIK3CA mutation was significantly associated with female sex and lower levels of tumor-infiltrating lymphocytes in 62/107 (57.94%) and 26/107 (30.23%) samples, respectively. KRAS and PIK3CA mutations did not significantly affect overall survival (120 months) in LS and non-LS patients. The high probability of LS in Indonesian CRC patients is associated with KRAS and PIK3CA mutations.

Efficient aerodynamic shape optimization by using unsupervised manifold learning to filter geometric features

Many aerodynamic shape optimization methods often focus on utilizing the end-to-end relationship between design variables and aerodynamic performance to find the optimal design, while overlooking the exploration of geometric knowledge of the shape itself. To fully use geometric knowledge to improve optimization efficiency, this paper proposes an efficient method by exploring the potential correlation between geometric features and aerodynamic performance at a low cost. We use unsupervised isometric feature mapping in manifold learning to capture geometric features that can distinguish the aerodynamic performance of different airfoils without embedding any tags. Then a filter criterion is establish based on the geometric features. During the optimization process, airfoils that deliver poor aerodynamic performance can be filtered out with a high probability before being precisely evaluated through computational fluid dynamics simulations. This helps improve samples quality to enhance the optimization efficiency. We applied the proposed method to the unconstrained and constrained optimizations of the Royal Aircraft Establishment (RAE) 2822 airfoil to validate its performance. The results demonstrate that the proposed method can improve the efficiency of optimization by over 50% compared with the original evolutionary optimization algorithm. It performs well across various optimization problems, demonstrating high engineering practical value.

Diagnostyka nietypowego stanu gorączkowego u 55-letniego mężczyzny

BackgroundThe paper describes a diagnostically challenging case of recurrent fever with an atypical course in a 55-year-old man. The authors highlight the significant difficulty in reaching a correct diagnosis, as well as the doubts and problems associated with the diagnostics. They suggest considering brucellosis as a diagnosis based on the patient's history and the course of the disease characterized by fluctuating, intermittent, and nocturnal fever.ObjectiveThe aim of the study was to present an atypical and diagnostically challenging case of recurrent febrile episodes in a 55-year-old man.Material and methodsA comprehensive diagnostic workup, including laboratory tests, imaging, and specialist consultations, was conducted. The patient's medical history, physical examination, and various diagnostic tests were analyzed.ResultsIn a patient with recurrent episodes of fever, an infection with Brucella spp. was detected, which was effectively treated with long-term antibiotic therapy. Imaging and laboratory diagnostics, along with specialist consultations, helped rule out other potential causes of the symptoms. The patient achieved lasting improvement following the treatment.ConclusionsThere is a high probability that the patient was infected with Brucella bacteria. Diagnostic challenges and the rarity of the disease, considered non-existent in Poland, hinder prompt confirmation or exclusion of infection. The authors aimed to highlight the possibility of a higher frequency of brucellosis in Poland. They suggest that Brucella bacteria may still be present, causing chronic, unrecognized, recurrent fevers. Based on the case analysis, the authors indicate that the frequent occurrence of this disease in Poland might be higher than reported by statistics.