Mathematical modeling of brain metastases growth and response to therapies: A review.

Brain metastases (BMs) are the most common intracranial tumor type and a significant health concern, affecting approximately 10% to 30% of all oncological patients. Although significant progress is being made, many aspects of the metastatic process to the brain and the growth of the resulting lesions are still not well understood. There is a need for an improved understanding of the growth dynamics and the response to treatment of these tumors. Mathematical models have been proven valuable for drawing inferences and making predictions in different fields of cancer research, but few mathematical works have considered BMs. This comprehensive review aims to establish a unified platform and contribute to fostering emerging efforts dedicated to enhancing our mathematical understanding of this intricate and challenging disease. We focus on the progress made in the initial stages of mathematical modeling research regarding BMs and the significant insights gained from such studies. We also explore the vital role of mathematical modeling in predicting treatment outcomes and enhancing the quality of clinical decision-making for patients facing BMs.

The relationship between levels of physical activity and participation in everyday life in stroke survivors: A systematic review and meta-analysis.

BACKGROUND: Stroke survivors demonstrate decreased physical activity (PA) and take time to return to participation in everyday life, but the relationship between the two variables is unknown. OBJECTIVE: To investigate the correlation and trajectory over time between levels of PA and participation in everyday life in stroke survivors. METHODS: PubMed, Web of Science, Scopus, SPORTDiscus, Rehabilitation&Sport Medicine Source, and PEDro databases were searched from inception to January 2024. Cross-sectional and prospective studies evaluating both levels of PA and participation in stroke survivors were included. Two reviewers independently conducted the study selection, data extraction, and quality assessment. Meta-analyses of pooled correlation coefficients were calculated when at least two studies reported a correlation coefficient between the same PA and participation outcomes. RESULTS: Of 4962 studies identified, 49 were included in the systematic review. Studies were rated high (55%%) or fair (45%) quality. A wide range of monitoring methodologies for assessing PA and participation were found in the 23 prospective studies. Seven studies were included in the meta-analyses, showing a positive moderate correlation between PA time and participation in activities of daily living (n = 148; r = 0.52; P < 0.01; I2 = 81%) in participants <6 months post-stroke, and between PA time and the participation in all areas (n = 126; r = 0.44; P < 0.01; I2 = 0%) in participants ≥6 months post-stroke. Overall, while PA showed significant improvements over time, participation only showed a tendency. CONCLUSIONS: Despite the heterogeneity, consistent positive associations were found between PA time and participation levels in some areas. Establishing consensus is crucial to reduce heterogeneity and facilitate data pooling.

New Monoterpenoid as the Sex Pheromone of Spanish Populations of the Longtailed Mealybug Pseudococcus Longispinus (Hemiptera: Pseudococcidae).

Pseudococcus longispinus (Targioni-Tozzetti) (Hemiptera: Coccoidea: Pseudococcidae), a polyphagous and cosmopolitan pest native to Australia, is a highly damaging pest for numerous crops of economic importance. The sex pheromone of this species (2-(1,5,5-trimethylcyclopent-2-en-1-yl)ethyl acetate), currently used for pest monitoring purposes, was not attractive to males in field experiments conducted in Spanish persimmon orchards infested with this mealybug. The virgin and mated female volatile profiles of these P. longispinus populations were studied by the volatile collection of effluvia in Porapak-Q. The resulting extracts were analyzed by gas chromatography coupled to mass spectrometry (GC-MS), revealing a new compound specific to virgin females and different from the previously described sex pheromone. Based on GC-MS data and nuclear magnetic resonance experiments, we envisaged monoterpene 2-(1,5-dimethyl-4-methylenecyclopent-2-en-1-yl)ethyl acetate as the new sex pheromone candidate, which was synthesized and shown to be attractive in the field to P. longispinus males of the Spanish population.

The fatty acid omega hydroxylase genes (CYP4 family) in the progression of metabolic dysfunction-associated steatotic liver disease (MASLD): An RNA sequence database analysis and review.

Fatty acid omega hydroxylase P450s consist of enzymes that hydroxylate various chain-length saturated and unsaturated fatty acids (FAs) and bioactive eicosanoid lipids. The human cytochrome P450 gene 4 family (CYP4) consists of 12 members that are associated with several human diseases. However, their role in the progression of metabolic dysfunction-associated fatty liver disease (MASLD) remains largely unknown. It has long been thought that the induction of CYP4 family P450 during fasting and starvation prevents FA-related lipotoxicity through FA metabolism to dicarboxylic acids that are chain-shortened in peroxisomes and then transported to the mitochondria for complete oxidation. Several studies have revealed that peroxisome succinate transported to the mitochondria is used for gluconeogenesis during fasting and starvation, and recent evidence suggests that peroxisome acetate can be utilized for lipogenesis and lipid droplet formation as well as epigenetic modification of gene transcription. In addition, omega hydroxylation of the bioactive eicosanoid arachidonic acid to 20-Hydroxyeicosatetraenoic acid (20-HETE) is essential for activating the GPR75 receptor, leading to vasoconstriction and cell proliferation. Several mouse models of diet-induced MASLD have revealed the induction of selective CYP4A members and the suppression of CYP4F during steatosis and steatohepatitis, suggesting a critical metabolic role in the progression of fatty liver disease. Thus, to further investigate the functional roles of CYP4 genes, we analyzed the differential gene expression of 12 members of CYP4 gene family in datasets from the Gene Expression Omnibus (GEO) from patients with steatosis, steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. We also observed the differential expression of various CYP4 genes in the progression of MASLD, indicating that different CYP4 members may have unique functional roles in the metabolism of specific FAs and eicosanoids at various stages of fatty liver disease. These results suggest that targeting selective members of the CYP4A family is a viable therapeutic approach for treating and managing MASLD.

"Analysis of Macular Pigment Optical Density in Childhood: A Systematic Review".

PURPOSE: This systematic review studies the relationship between Macular Pigment Optical Density (MPOD) values and cognitive and visual function in childhood. METHODS: It included cross-sectional, observational studies or controlled clinical trials in humans between 0 and 18 years of age, analyzing MPOD values in 3 main databases: PubMed, Scopus and Web of Science. The study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement recommendations. RESULTS: Thirteen studies were included in this systematic review. The relationship of cognitive function, visual function and diverse variables with MPOD was analyzed in 4, 4 and 5 studies, respectively. The age of the participants ranged between premature infants to 12 years. Most of the studies used Heterochromatic Flicker Photometry (HFP) with macular densitometer to obtain MPOD values. MPOD values ranged between 0 (undetectable) to 0.66 ± 0.03 d.u. Only 4 articles studied the relationship between MPOD values and dietary intake of lutein and zeaxanthin using questionnaires about diet. CONCLUSIONS: Lutein and zeaxanthin accumulation plays an important role during the maturational stage and childhood development. Although cognitive function is more strongly correlated with MPOD values, the relationship with visual function remains unclear, and further studies are required to support this relationship.

Opioid Overdoses and Take-Home Naloxone Interventions: Ethnographic Evidence for Individual-Level Barriers to Treatment of Opioid Use Disorders in Rural Appalachia.

Introduction: Research indicates that take-home naloxone (THN) is saving lives across rural Appalachia, but whether it also results in treatment for opioid use disorders (OUDs) remains unclear. This study involves a detailed qualitative analysis of interviews with 16 individuals who had overdosed on opioids 61 times to understand why a THN intervention does not routinely lead to OUD treatment. Methods: This study builds upon a one-year (2018) qualitative study on community responses to opioid overdose fatalities in four adjacent rural counties in Western Pennsylvania. Using a semi-structured interview guide, 16 individuals who had experienced one or more overdoses were interviewed. Using NVivo, the transcribed audio-recorded interviews were coded, and a thematic analysis of the coded text was conducted. Findings: Findings reveal that of the 29 overdoses that included a THN intervention, only eight resulted in treatment. The analysis derives five individual-level barriers to treatment: (1) opioid dependence, (2) denial/readiness, (3) opioid withdrawal fears, (4) incarceration concerns, and (5) stigma and shame. These barriers impeded treatment, even though all the interviewees knew of treatment programs, how to access them, and in some cases had undergone treatment previously. Discussion and Conclusion: findings indicate that there is evidence that the five barriers make entering treatment after a THN intervention challenging and seemingly insurmountable at times. Recommendations based on the findings include increasing efforts to reduce stigma of OUDs in the community, including self-stigma resulting from misusing opioids, increasing informational efforts about Good Samaritan Laws, and increasing familiarity with medication-assisted treatments for OUDS.

(F)utility of preoperative pulmonary function testing in pectus excavatum to assess severity.

PURPOSE: The utility of pulmonary function testing (PFT) in pectus excavatum (PE) has been subject to debate. Although some evidence shows improvement from preoperative to postoperative values, the clinical significance is uncertain. A high failure-to-completion rate for operative PFT (48%) was identified in our large institutional cohort. With such a high non-completion rate, we questioned the overall utility of PFT in the preoperative assessment of PE and sought to evaluate if other measures of PE severity or cardiopulmonary function could explain this finding. METHODS: Demographics, clinical findings, and results from cardiac MRI, PFT (spirometry and plethysmography), and cardiopulmonary exercise tests (CPET) were reviewed in 270 patients with PE evaluated preoperatively between 2015 and 2018. Regression modeling was used to measure associations between PFT completion and cardiopulmonary function. RESULTS: There were no differences in demographics, symptoms, connective tissue disorders, or multiple indices of pectus severity and cardiac deformation in PFT completers versus non-completers. While regression analysis revealed higher RVEF, LVEF, and LVEF-Z scores, lower RV-ESV/BSA, LV-ESV/BSA, and LV-ESV/BSA-Z scores, and abnormal breathing reserve in PFT completers vs. non-completers, these findings were not consistent across continuous and binary analyses. CONCLUSIONS: We found that PFT completers were not significantly different from non-completers in most structural and functional measures of pectus deformity and cardiopulmonary function. Inability to complete PFT is not an indicator of pectus severity.

Recovery of spatio-temporal gait and functional parameters following unilateral eccentric exercise-induced muscle damage in the hamstrings.

OBJECTIVES: This study aimed to analyze how spatiotemporal gait parameters, active knee extension range of motion, muscle activity, and self-perceived function change over a seven-day period in healthy individuals after exercise-induced muscle damage (EIMD) in the hamstrings. DESIGN: Longitudinal cohort study. METHODS: Twenty-four healthy males participated in four sessions before and after EIMD (pre-EIMD, 48 h, 96 h, and 168 h post-EIMD). A single-leg deadlift exercise was performed to provoke EIMD in the hamstrings of the dominant leg. Lower limb function perception, spatiotemporal gait parameters, active knee extension range of motion, and electromyographic (EMG) activity of the semitendinosus and biceps femoris muscles during gait and maximal isometric contraction were assessed bilaterally. RESULTS: At 48 h, the EIMD-side showed reduced step length, active knee extension range of motion, maximal strength and EMG activity compared to baseline (P < 0.042), while increased relative EMG activity in the biceps femoris during gait (P = 0.001). At 96 h, step length and EMG activity on the EIMD-side reached similar values to those at baseline, whereas lower limb function perception and active knee extension range of motion returned to baseline state at 168 h post-EIMD. No changes over time were observed on the control-side. CONCLUSIONS: Recovery from EIMD requires a multimodal assessment since the different parameters affected by EIMD recover at different paces. Active range of motion appears to be the last variable to fully recover. Self-perceived function should not be considered in isolation as it does not represent complete functional recovery.

Psychophysiological evaluation of the Smartick method in children with reading and mathematical difficulties.

Introduction: Assistive technologies for learning are aimed at promoting academic skills, such as reading and mathematics. These technologies mainly embrace mobile and web apps addressed to children with learning difficulties. Nevertheless, most applications lack pedagogical foundation. Additionally, the task of selecting suitable technology for educational purposes becomes challenging. Hence, this protocol posits the psychophysiological assessment of an online method for learning (OML) named Smartick. This platform comprises reading and math activities for learning training. In this protocol, individual monitoring of each child is proposed to determine the progress in learning caused by Smartick. Methods and analysis: One hundred and twelve children aged between 8 and 12 who present reading or math difficulty after a rigorous psychometric evaluation will be recruited. The study comprises four sessions. In sessions 1 and 2, collective and individual psychometric evaluations will be performed, respectively. Reading and mathematical proficiency will be assessed, as well as attentional levels and intellectual quotient. Subsequently, each child will be semi-randomly assigned to either the experimental or control groups. Afterward, a first EEG will be collected for all children in session 3. Then, experimental groups will use Smartick for 3 months, in addition to their traditional learning method. In contrast, control groups will only continue with their traditional learning method. Finally, session 4 will consist of performing a second psychometric evaluation and another EEG, so that psychophysiological parameters can be encountered that indicate learning improvements due to the OML, regardless of the traditional learning method at hand. Discussion: Currently, few studies have validated learning improvement due to assistive technologies for learning. However, this proposal presents a psychophysiological evaluation addressed to children with reading or math difficulties who will be trained with an OML.

Dual-Time-Point 18F-FDG PET/CT in Infective Endocarditis: Impact of Delayed Imaging in the Definitive Diagnosis of Endocarditis.

Infective endocarditis (IE) is a major public health condition due to the associated high morbidity and mortality. Our objective was to evaluate the utility of dual-time 2-deoxy-2-[18F] fluoro-D-glucose (18F-FDG) Positron Emission Tomography/Computed Tomography (PET/CT) imaging in the diagnosis of active IE in patients with suspected native valve endocarditis (NVE) and prosthetic valve endocarditis (PVE). For this purpose, a retrospective study was carried out, including patients suspicious of NVE or PVE who underwent a dual-time-point 18F-FDG PET/CT. A final diagnosis was established by the Endocarditis Team after patient follow-up using all the available findings. Sixty-nine patients were assessed. A final diagnosis of NVE was established in 3 patients of the 34 by 18F-FDG PET/CT and in the case of PVE was established in 20 patients of the 35. A statistically significant association was found when evaluating the association between PET diagnosis at early acquisition and final diagnosis of IE (χ2 = 30.198, p < 0.001) and PET diagnosis at delayed acquisition for final diagnosis of IE (χ2 = 9.412, p = 0.002). Delayed PET/CT imaging determined the IE diagnosis in 16/58 of the studies. In conclusion, delayed 18F-FDG PET/CT imaging seems to be useful in improving the definitive diagnosis of IE.

Assessment of the Impact of Humic Acids on Intestinal Microbiota, Gut Integrity, Ileum Morphometry, and Cellular Immunity of Turkey Poults Fed an Aflatoxin B1-Contaminated Diet.

A recent study published data on the growth performance, relative weights of the organs of the gastrointestinal tract, liver histology, serum biochemistry, and hematological parameters for turkey poults fed an experimental diet contaminated with aflatoxin B1 (AFB1) and humic acids (HA) extracted from vermicompost. The negative effects of AFB1 (250 ng AFB1/g of feed) were significantly reduced by HA supplementation (0.25% w/w), suggesting that HA might be utilized to ameliorate the negative impact of AFB1 from contaminated diets. The present study shows the results of the remaining variables, as an extension of a previously published work which aimed to evaluate the impact of HA on the intestinal microbiota, gut integrity, ileum morphometry, and cellular immunity of turkey poults fed an AFB1-contaminated diet. For this objective, five equal groups of 1-day-old female Nicholas-700 turkey poults were randomly assigned to the following treatments: negative control (basal diet), positive control (basal diet + 250 ng AFB1/g), HA (basal diet + 0.25% HA), HA + AFB1 (basal diet + 0.25% HA + 250 ng AFB1/g), and Zeolite (basal diet + 0.25% zeolite + 250 ng AFB1/g). In the experiment, seven replicates of ten poults each were used per treatment (n = 70). In general, HA supplementation with or without the presence of AFB1 showed a significant increase (p < 0.05) in the number of beneficial butyric acid producers, ileum villi height, and ileum total area, and a significant reduction in serum levels of fluorescein isothiocyanate-dextran (FITC-d), a marker of intestinal integrity. In contrast, poults fed with AFB1 showed a significant increase in Proteobacteria and lower numbers of beneficial bacteria, clearly suggesting gut dysbacteriosis. Moreover, poults supplemented with AFB1 displayed the lowest morphometric parameters and the highest intestinal permeability. Furthermore, poults in the negative and positive control treatments had the lowest cutaneous basophil hypersensitivity response. These findings suggest that HA supplementation enhanced intestinal integrity (shape and permeability), cellular immune response, and healthier gut microbiota composition, even in the presence of dietary exposure to AFB1. These results complement those of the previously published study, suggesting that HA may be a viable dietary intervention to improve gut health and immunity in turkey poults during aflatoxicosis.

Uncovering a novel mechanism: Butyrate induces estrogen receptor alpha activation independent of estrogen stimulation in MCF-7 breast cancer cells.

Butyrate is a promising candidate for an antitumoral drug, as it promotes cancer cell apoptosis and reduces hormone receptor activity, while promoting differentiation and proliferation in normal cells. However, the effects of low-dose butyrate on breast cancer cell cultures are unclear. We explored the impact of sub-therapeutic doses of butyrate on estrogen receptor alpha (ERα) transcriptional activity in MCF-7 cells, using RT-qPCR, Western blot, wound-healing assays, and chromatin immunoprecipitation. Our results showed that sub-therapeutic doses of sodium butyrate (0.1 - 0.2 mM) increased the transcription of ESR1, TFF1, and CSTD genes, but did not affect ERα protein levels. Moreover, we observed an increase in cell migration in wound-healing assays. ChIP assays revealed that treatment with 0.1 mM of sodium butyrate resulted in estrogen-independent recruitment of ERα at the pS2 promoter and loss of NCoR. Appropriate therapeutic dosage of butyrate is essential to avoid potential adverse effects on patients' health, especially in the case of estrogen receptor-positive breast tumors. Sub-therapeutic doses of butyrate may induce undesirable cell processes, such as migration due to low-dose butyrate-mediated ERα activation. These findings shed light on the complex effects of butyrate in breast cancer and provide insights for research in the development of antitumoral drugs.

Training pathologists to assess stromal tumour-infiltrating lymphocytes in breast cancer synergises efforts in clinical care and scientific research.

A growing body of research supports stromal tumour-infiltrating lymphocyte (TIL) density in breast cancer to be a robust prognostic and predicive biomarker. The gold standard for stromal TIL density quantitation in breast cancer is pathologist visual assessment using haematoxylin and eosin-stained slides. Artificial intelligence/machine-learning algorithms are in development to automate the stromal TIL scoring process, and must be validated against a reference standard such as pathologist visual assessment. Visual TIL assessment may suffer from significant interobserver variability. To improve interobserver agreement, regulatory science experts at the US Food and Drug Administration partnered with academic pathologists internationally to create a freely available online continuing medical education (CME) course to train pathologists in assessing breast cancer stromal TILs using an interactive format with expert commentary. Here we describe and provide a user guide to this CME course, whose content was designed to improve pathologist accuracy in scoring breast cancer TILs. We also suggest subsequent steps to translate knowledge into clinical practice with proficiency testing.

Bacillus subtilis stress-associated mutagenesis and developmental DNA repair.

SUMMARYThe metabolic conditions that prevail during bacterial growth have evolved with the faithful operation of repair systems that recognize and eliminate DNA lesions caused by intracellular and exogenous agents. This idea is supported by the low rate of spontaneous mutations (10-9) that occur in replicating cells, maintaining genome integrity. In contrast, when growth and/or replication cease, bacteria frequently process DNA lesions in an error-prone manner. DNA repairs provide cells with the tools needed for maintaining homeostasis during stressful conditions and depend on the developmental context in which repair events occur. Thus, different physiological scenarios can be anticipated. In nutritionally stressed bacteria, different components of the base excision repair pathway may process damaged DNA in an error-prone approach, promoting genetic variability. Interestingly, suppressing the mismatch repair machinery and activating specific DNA glycosylases promote stationary-phase mutations. Current evidence also suggests that in resting cells, coupling repair processes to actively transcribed genes may promote multiple genetic transactions that are advantageous for stressed cells. DNA repair during sporulation is of interest as a model to understand how transcriptional processes influence the formation of mutations in conditions where replication is halted. Current reports indicate that transcriptional coupling repair-dependent and -independent processes operate in differentiating cells to process spontaneous and induced DNA damage and that error-prone synthesis of DNA is involved in these events. These and other noncanonical ways of DNA repair that contribute to mutagenesis, survival, and evolution are reviewed in this manuscript.

Nuevo índice aterogénico para la predicción de aterosclerosis carotídea basado en la ratio proteína C reactiva no ultrasensible/HDL / New atherogenic index for the prediction of carotid atherosclerosis based on the non-ultrasensitive c-reactive protein/HDL ratio

Introducción La valoración del riesgo cardiovascular aparece en las guías clínicas como medida de prevención de enfermedades cardiovasculares, cuya etiología fundamental es la arteriosclerosis. Una de las herramientas que se utiliza para estimar el riesgo en práctica clínica son los índices aterogénicos (IA), cocientes entre fracciones lipídicas con rangos de referencia bien establecidos. A pesar de su uso extendido, existe todavía información limitada sobre su utilidad clínica. En los últimos años, algunas investigaciones han reforzado el papel de la inflamación en la etiología y cronicidad del proceso aterosclerótico. La inclusión de parámetros inflamatorios en el cálculo de IA podría mejorar su rendimiento diagnóstico en la detección de arteriosclerosis. Nos propusimos evaluar un nuevo IA en forma de ratio entre los valores de proteína C reactiva (PCR) no ultrasensible y las cifras de colesterol unido a lipoproteínas de alta densidad (HDL). Métodos Se incluyeron en el estudio 282 pacientes, asintomáticos, y sin historia de enfermedad cardiovascular. Se realizó en todos ellos analítica con perfil lipídico y PCR, y en el plazo inferior a un mes, ecografía carotídea para evaluar la presencia de ateromatosis. El nuevo IA se estableció como el cociente entre el valor de PCR no ultrasensible en mg/dL (multiplicado por 100) y el valor de HDL en mg/dL. Se comparó con los índices de Castelli I y II, y el índice aterogénico del plasma. La curva ROC determinó que el punto de corte óptimo del nuevo IA fue valor=1, con un área bajo la curva de 0,678 (IC 95% 0,60-0,75; p<0,001). ResultadosLa edad media de la muestra fue 60,4±14,5 años. Un total de 118 pacientes (41,8% del total) tenían arteriosclerosis carotídea. Al evaluar el rendimiento diagnóstico de los IA, encontramos que la ratio PCR·100/HDL mostró los valores más elevados de sensibilidad y valor predictivo positivo (0,73 y 0,68, respectivamente) ... Conclusiones... (AU)

Introduction Current guidelines recommend cardiovascular risk assessment as a preventive measure for cardiovascular diseases, whose fundamental etiology is arteriosclerosis. One of the tools used to estimate risk in clinical practice are atherogenic indices (AI), ratios between lipid fractions with well-established reference ranges. Despite its widespread use, there is still limited information on its clinical utility. In recent years, some research has reinforced the role of inflammation in the etiology and chronicity of the atherosclerotic process. The inclusion of inflammatory parameters in the AI calculation could improve its diagnostic performance in the detection of arteriosclerosis. We sought to evaluate a new AI as a ratio between C-reactive protein (CRP) values and high-density lipoprotein cholesterol (HDL) values. Methods A total of 282 asymptomatic patients with no history of cardiovascular disease were included in the study. Laboratory tests with lipid profile and CRP, and carotid ultrasound to assess the presence of atheromatosis were performed in all of them. The new AI is established as the ratio between non-ultrasensitive CRP value in mg/dL (multiplied by 100) and HDL value in mg/dL. It was compared with the Castelli I and II indices, and the plasma atherogenic index. The optimal cut-off point of the new AI was value=1 as determined by ROC curve, with an area under the curve of 0.678 (95% CI 0.60-0.75; p<0.001).Results Mean age of patients was 60.4±14.5 years. A total of 118 patients (41.8% of total) had carotid arteriosclerosis. When evaluating the diagnostic performance of different AIs, we found that CRP·100/HDL ratio showed the highest values of sensitivity and positive predictive value (0.73 and 0.68, respectively) compared to the Castelli I and II indices, and the plasma atherogenic index. ... Conclusions ... (AU)

Cortical and subcortical microstructure integrity changes after repetitive transcranial magnetic stimulation therapy in cocaine use disorder and relates to clinical outcomes.

Cocaine use disorder (CUD) is a worldwide public health condition that is suggested to induce pathological changes in macrostructure and microstructure. Repetitive transcranial magnetic stimulation (rTMS) has gained attention as a potential treatment for CUD symptoms. Here, we sought to elucidate whether rTMS induces changes in white matter (WM) microstructure in frontostriatal circuits after 2 weeks of therapy in patients with CUD and to test whether baseline WM microstructure of the same circuits affects clinical improvement. This study consisted of a 2-week, parallel-group, double-blind, randomized controlled clinical trial (acute phase) (sham [n = 23] and active [n = 27]), in which patients received two daily sessions of rTMS on the left dorsolateral prefrontal cortex (lDLPFC) as an add-on treatment. T1-weighted and high angular resolution diffusion-weighted imaging (DWI-HARDI) at baseline and 2 weeks after served to evaluate WM microstructure. After active rTMS, results showed a significant increase in neurite density compared with sham rTMS in WM tracts connecting lDLPFC with left and right ventromedial prefrontal cortex (vmPFC). Similarly, rTMS showed a reduction in orientation dispersion in WM tracts connecting lDLPFC with the left caudate nucleus, left thalamus, and left vmPFC. Results also showed a greater reduction in craving Visual Analogue Scale (VAS) after rTMS when baseline intra-cellular volume fraction (ICVF) was low in WM tracts connecting left caudate nucleus with substantia nigra and left pallidum, as well as left thalamus with substantia nigra and left pallidum. Our results evidence rTMS-induced WM microstructural changes in fronto-striato-thalamic circuits and support its efficacy as a therapeutic tool in treating CUD. Further, individual clinical improvement may rely on the patient's individual structural connectivity integrity.

Neuroendocrine Tumor Presented With Axillary Mass: A Case Report.

ABSTRACT: A 79-year-old man presented with a palpable left axillary mass and ultrasonography findings of conglomerate lymph nodes. The initial clinical suspicion was a lymphoproliferative disorder, but histopathological results revealed a grade 3 neuroendocrine tumor. The mass showed somatostatin receptor overexpression in 99m Tc-HYNIC-TOC scintigraphy and high uptake in 18 F-FDG PET/CT. Bilateral hypermetabolic adrenal nodes suggestive of metastases were also detected. The patient was treated with chemotherapy and immunotherapy, and PET/CT scan showed a partial metabolic response after 4 cycles. According to this case, neuroendocrine tumor should be considered in the differential diagnosis of axillary masses.

A Hybrid Cryptosystem Incorporating a New Algorithm for Improved Entropy.

Today, safeguarding sensitive content through encryption is crucial. This work presents a hybrid cryptosystem for images that employs both asymmetric and symmetric encryption. The asymmetric component involves applying the Diffie-Hellman protocol and the ElGamal cryptosystem to securely transmit two constants. These constants are necessary for the symmetrical aspect to generate dynamic permutations, substitution boxes, and round keys. Following an encryption process with fourteen rounds, the encrypted images are processed by an algorithm proposed to enhance entropy, a critical metric for assessing encryption quality. It increases the frequencies of the basic colors to achieve a histogram closely resembling a uniform distribution, but it increases the image size by approximately 8%. This improves the entropy values achieved by the hybrid cryptosystem, bringing them remarkably close to the ideal value of 8.0. In specific instances, the entropy values were elevated from 7.99926 to 8.0. The proposed method exhibits resilience against various attacks, including differential, linear, brute force, and algebraic attacks, as evaluated through the entropy, correlation, goodness of fit, Discrete Fourier Transform (DFT), Number of Pixels Change Rate (NPCR), Unified Average Changing Intensity (UACI), Avalanche Criteria (AC), contrast, energy, and homogeneity. Further, encrypted images are subjected to noise attacks ranging from 20% to 50% noise, including additive, multiplicative, occlusion noise, as well as the newly introduced χ2 noise. The noise damage is quantified using the proposed Similarity Parameter (SP), and a 3 × 3 median filter is employed to enhance the visual quality.

Extracellular lactate as an alternative energy source for retinal bipolar cells.

Retinal bipolar and amacrine cells receive visual information from photoreceptors and participate in the first steps of image processing in the retina. Several studies have suggested the operation of aerobic glycolysis and a lactate shuttle system in the retina due to the high production of this metabolite under aerobic conditions. However, whether bipolar cells form part of this metabolic circuit remains unclear. Here, we show that the monocarboxylate transporter 2 is expressed and functional in inner retinal neurons. Additionally, we used genetically encoded FRET nanosensors to demonstrate the ability of inner retinal neurons to consume extracellular lactate as an alternative to glucose. In rod bipolar cells, lactate consumption allowed cells to maintain the homeostasis of ions and electrical responses. We also found that lactate synthesis and transporter inhibition caused functional alterations and an increased rate of cell death. Overall, our data shed light on a notable but still poorly understood aspect of retinal metabolism.

Overexpression of Endoplasmic Reticulum Proteins from Arabidopsis thaliana in Baculovirus.

The overproduction of proteins of the endoplasmic reticulum (ER) of plant cells in prokaryotic heterologous gene expression system remains a technical challenge. Recent advances in genetically modified insect cell technology and virus engineering methods have paved the way to produce recombinant ER plant proteins, including those harboring posttranslational modifications, and therefore, to yield ER plant proteins that are natively folded and fully functional. The present contribution focuses on the baculovirus-expression system flashBAC, which overcomes certain technical hurdles found in other insect cell-based expression systems such as the generation of a bacmid and the negative selection of recombinant clones.