Endoscopic ultrasound-guided tissue acquisition for focal liver lesions in patients with a history of multiple primary malignant neoplasms.

Objective: This study aimed to investigate the usefulness of endoscopic ultrasound-guided tissue acquisition (EUS-TA) for diagnosing focal liver lesions in patients with a history of multiple primary malignant neoplasms. Methods: Among patients who underwent EUS-TA for focal liver lesions between 2016 and 2022, those with a history of multiple malignant neoplasms were included. A histologically confirmed malignant tumor within the past 5 years before EUS-TA was defined as a history of malignant neoplasm. The primary outcomes were diagnostic ability and adverse events of EUS-TA. Results: This study included 16 patients (median age, 73 [33-90] years), the median tumor size was 32 (6-51) mm, 14 had a history of double malignant neoplasms, whereas two had triple malignant neoplasms. Malignant neoplasms were detected histologically or cytologically in all cases. Immunohistochemistry was performed in 75% (12/16), and the final diagnosis of EUS-TA was metastatic liver tumor in 12 patients, and primary malignant liver tumor in four patients. The primary site could be identified in 11 of 12 metastatic tumor cases. The diagnostic yield of EUS-TA was 100% (16/16) for differentiating benign and malignant tumors and 94% (15/16) for confirming the histological type including the primary site of metastatic lesions. No adverse events were associated with the procedure. Conclusion: EUS-TA is a useful diagnostic modality for focal liver lesions in patients with a history of multiple malignant neoplasms, allowing for the differential diagnosis of primary and metastatic tumors and identification of the primary site of metastatic lesions.

Determination of double bond positions in unsaturated fatty acids by pre-column derivatization with dimethyl and dipyridyl disulfide followed by LC-SWATH-MS analysis.

Comprehensive in-depth structural characterization of free mono-unsaturated and polyunsaturated fatty acids often requires the determination of carbon-carbon double bond positions due to their impact on physiological properties and relevance in biological samples or during impurity profiling of pharmaceuticals. In this research, we report on the evaluation of disulfides as suitable derivatization reagents for the determination of carbon-carbon double bond positions of unsaturated free fatty acids by UHPLC-ESI-QTOF-MS/MS analysis and SWATH (sequential windowed acquisition of all theoretical mass spectra) acquisition. Iodine-catalyzed derivatization of C = C double bonds with dimethyl disulfide (DMDS) enabled detection of characteristic carboxy-terminal MS2 fragments for various fatty acids in ESI negative mode. The determination of double bond positions of fatty acids with up to three double bonds, the transfer of the method to plasma samples, and its limitations have been shown. To achieve charge-switching for positive ion mode MS-detection, derivatization with 2,2'-dipyridyldisulfide (DPDS) was investigated. It enabled detection of both corresponding characteristic omega-end- and carboxy-end-fragments for fatty acids with up to two double bonds in positive ion mode. It provides a straightforward strategy for designing MRM transitions for targeted LC-MS/MS assays. Both derivatization techniques represent a simple and inexpensive way for the determination of double bond positions in fatty acids with low number of double bonds. No adaptation of MS hardware is required and the specific isotopic pattern of resulting sulfur-containing products provides additional structural confirmation. This reaction scheme opens up the avenue of structural tuning of disulfide reagents beyond DMDS and DPDS using reagents like cystine and analogs to achieve enhanced performance and sensitivity.

P2X7 receptors modulate acquisition of cue fear extinction and contextual background memory generalization in male mice.

The purinergic P2X7 receptors (P2X7R) are activated by adenosine triphosphate (ATP) in several brain regions, particularly those involved with emotional control and the regulation of fear-related memories. Here, we investigate the role of P2X7R in fear learning memory, specifically in the acquisition and consolidation phases of the cued fear conditioning paradigm. C57Bl/6 wildtype (WT) male mice that received a single i.p. injection of the selective P2X7R antagonist A438079 prior the conditioning session showed generalization of cued fear memory and impaired fear extinction recall in the test session, while those treated prior the extinction session exhibited a similar behavior profile accompanied by resistance in the extinction learning. However, no effects were observed when this drug was administered immediately after the conditioning, extinction, or before the test session. Our results with P2X7R knockout (P2X7 KO) mice showed a behavioral profile that mirrored the collective effects observed across all pharmacological treatment conditions. This suggests that the P2X7R KO model effectively replicates the behavioral changes induced by the pharmacological interventions, demonstrating that we have successfully isolated the role of P2X7R in the fear and extinction phases of memory. These findings highlight the role of P2X7R in the acquisition and recall of extinction memory and supports P2X7R as a promising candidate for controlling abnormal fear processing, with potential applications for stress exposure-related disorders such as post-traumatic stress disorder (PTSD).

A temporal quantitative analysis of visuomotor behavior during four twisting somersaults in elite and sub-elite trampolinists.

Vision has previously been correlated with performance in acrobatic sports, highlighting visuomotor expertise adaptations. However, we still poorly understand the visuomotor strategies athletes use while executing twisting somersaults, even though this knowledge might be helpful for skill development. Thus, the present study sought to identify the differences in gaze behavior between elite and sub-elite trampolinists during the execution of four acrobatics of increasing difficulty. Seventeen inertial measurement units and a wearable eye-tracker were used to record the body and gaze kinematics of 17 trampolinists (8 elites, 9 sub-elites). Six typical metrics were analyzed using a mixed analysis of variance (ANOVA) with the Expertise as inter-subject and the Acrobatics as intra-subject factors. To complement this analysis, advanced temporal eye-tracking metrics are reported, such as the dwell time on areas of interest, the scan path on the trampoline bed, the temporal evolution of the gaze orientation endpoint (SPGO), and the time spent executing specific neck and eye strategies. A significant main effect of Expertise was only evidenced in one of the typical metrics, where elite athletes exhibited a higher number of fixations compared to sub-elites (p = 0.033). Significant main effects of Acrobatics were observed on all metrics (p < 0.05), revealing that gaze strategies are task-dependent in trampolining. The recordings of eyes and neck movements performed in this study confirmed the use of "spotting" at the beginning and end of the acrobatics. They also revealed a unique sport-specific visual strategy that we termed as self-motion detection. This strategy consists of not moving the eyes during fast head rotations, a strategy mainly used by trampolinists during the twisting phase. This study proposes a detailed exploration of trampolinists' gaze behavior in highly realistic settings and a temporal description of the visuomotor strategies to enhance understanding of perception-action interactions during the execution of twisting somersaults.

Characterization of the ferric uptake regulator VaFur regulon and its role in Vibrio anguillarum pathogenesis.

The Gram-negative marine bacterium Vibrio anguillarum is able to cause vibriosis with hemorrhagic septicemia in many fish species, and iron acquisition is a critical step for virulence. Despite the fact that genes specific to certain processes of iron transport have been studied, the iron-regulated circuits of the V. anguillarum strains remain poorly understood. In this study, we showed that in V. anguillarum strain 775, iron could affect the expression of a number of critical metabolic pathways and virulence factors. The global iron uptake regulator VaFur is the major actor to control these processes for the bacterium to respond to different iron conditions. A VaFur binding motif was identified to distinguish directly and indirectly regulated targets. The absence of VaFur resulted in the aberrant expression of most iron acquisition determinants under rich-iron conditions. A similar regulation pattern was also observed in the transcription of genes coding for the type VI secretion system. The expression of peroxidase genes is positively controlled by VaFur to prevent iron toxicity, and the deletion of Vafur caused impaired growth in the presence of iron and H2O2. VaFur also upregulates some virulence factors under limited-iron conditions, including metalloprotease EmpA and motility, which are likely critical for the high virulence of V. anguillarum 775. The deletion of VaFur led to reduced swimming motility and decreased extracellular protease activity under limited-iron conditions, thereby leading to attenuated pathogenicity. Our study provides more evidence to better understand the VaFur regulon and its role in the pathogenesis of V. anguillarum.IMPORTANCEVibriosis, the most common disease caused by marine bacteria belonging to the genus Vibrio, leads to massive mortality of economical aquatic organisms in Asia. Iron is one of the most important trace elements, and its acquisition is a critical battle occurring between the host and the pathogen. However, excess iron is harmful to cells, so iron utilization needs to be strictly controlled to adapt to different conditions. This process is mediated by the global iron uptake regulator Fur, which acts as a repressor when iron is replete. On the other hand, free iron in the host is limited, so the reduced virulence of the Δfur mutant should not be directly caused by abnormally regulated iron uptake. The significance of this work lies in uncovering the mechanism by which the deletion of Fur causes reduced virulence in Vibrio anguillarum and identifying the critical virulence factors that function under limited-iron conditions.

Phosphorus acquisition, translocation, and redistribution in maize.

Phosphorus (P) is an essential nutrient for crop growth, making it important for maintaining food security as the global population continues to increase. Plants acquire P primarily via the uptake of inorganic phosphate (Pi) in soil through their roots. Pi, which is usually sequestered in soils, is not easily absorbed by plants and represses plant growth. Plants have developed a series of mechanisms to cope with P deficiency. Moreover, P fertilizer applications are critical for maximizing crop yield. Maize is a major cereal crop cultivated worldwide. Increasing its P-use efficiency is important for optimizing maize production. Over the past two decades, considerable progresses have been achieved in research aimed at adapting maize varieties to changes in environmental P supply. Here, we present an overview of the morphological, physiological, and molecular mechanisms involved in P acquisition, translocation, and redistribution in maize, and combine the advances in Arabidopsis and rice, to better elucidate the progress of P nutrition. Additionally, we summarize the correlation between P and abiotic stress responses. Clarifying the mechanisms relevant to improving P absorption and use in maize can guide future research on sustainable agriculture.

Optimizing Learning Outcomes when Teaching Sight Words using Fruits and Vegetables as Reinforcers.

Reinforcers frequently chosen may not offer the same nutritional value as fruits and vegetables. Prior researchers have explored preferences and the effectiveness of salty and sweet foods compared to fruits and vegetables, but the criteria for demonstrating effectiveness have often been arbitrary rather than academic. In addition, it remains unclear how the integration of these potentially nutritious reinforcers might affect learning or hinder learning efficiency. Therefore, the objective of this study was to investigate whether introducing fruits or vegetables as potential reinforcers could sustain responding achieved with salty or sweet reinforcers. The implications of this model for incorporating a variety of reinforcers while maintaining responding are also discussed.

Towards active health: A study on the relationship between physical activity and body image among college students.

Aims: Active health is a new concept, model, and system for maintaining a state of whole-person health. In the context of the increasing severity of college students' mental health, it is of great significance to explore the relationship between physical activity and college students' body image based on an active health perspective. Methods: A survey was conducted among 853 college students in Zhejiang province using the physical activity rating scale, body image scale, sense of acquisition of sports body shaping scale and social adjustment scale. Using SPSS25.0 and Amos 24.0 software for data processing and analysis. Results: (1) There is a significant positive correlation between physical activity, body image, sense of acquisition of sports body shaping, and social adjustment. There is a significant positive correlation between physical activity and body image among college students; The sense of acquisition of sports body shaping a significant mediating role between physical activity and the promotion of college students' body image. The effects of physical activity on body image were mainly achieved through the following three mediating pathways: (1) physical activity → sense of acquisition of sports body shaping → body image, the mediating effect value of this pathway was 0.18, which accounted for 31.6 % of the total effect, with a confidence interval of [0.08, 0.28], (2) physical activity → social adaptation → body image, the mediating effect value of this pathway was 0.09, which accounted for 15.8 % of the total effect of 15.8 %, with a confidence interval of [0.03, 0.15], and (3) physical activity → sense of acquisition of sports body shaping → social adaptation → body image, a pathway with a mediated effect value of 0.09, accounting for 15.8 % of the total effect, with a confidence interval of [0.01, 0.17]. Conclusions: Physical activity is an important factor in promoting the body image of college students, and there is a chain intermediary effect between physical activity and body image. School sport has its own disciplinary value and unique strengths in advancing the development of body image in adolescents, and the significant mediating effects of sense of acquisition of sports body shaping and social adaptation in this process provide theoretical support for the body image turn to move from theory to practice in the field of school sport.

A study method using early dynamic acquisition of [18F]fluorodopa positron emission tomography for the differential diagnosis between progression and radionecrosis of brain metastases after radiotherapy.

BACKGROUND: It is difficult to distinguish between the brain metastasis progression (BMP) and brain radionecrosis (BRN) on the basis of 18F-3,4-dihydroxyphenylalanine positron emission tomography/computed-tomography (18F-FDOPA PET/CT) data. The advent of silicon photomultiplier (SiPM) PET technology makes it possible to study dynamic volumes and potentially improve diagnostic accuracy. We developed a method for processing 18F-FDOPA PET/CT in the differential diagnosis between BMP and BRN. The method involves a short (3-second) sampling time during a 4-minute acquisition on a SiPM-PET/CT machine. We prospectively included 15 patients and 19 metastases. All acquisitions were performed in list mode acquisition for 25 min on a four-ring SiPM PET/CT system. We calculated the ratios between the maximum activity in the lesion's voxel and the mean activity in the contralateral region (VOImax/CLmean) or the mean activity in the white matter (VOImax/WMmean). RESULTS: Seven lesions were classified as BMP and twelve were classified as BRN. Statistically significant intergroup differences in the VOImax/CLmean and VOImax/WMmean activity ratios were observed for both the clinical volume and the early acquisition. The best performing quantitative variable was the VOImax/CLmean ratio on early acquisition, with a diagnostic accuracy of 94.7%, a sensitivity of 100%, and a specificity of 91.7%. CONCLUSION: The 18F-FDOPA PET/CT data acquired a few minutes after the bolus injection confirms its value in differentiating between BMP and BRN, compared to the much longer classic clinical protocol.

Example-based learning in heuristic domains: can using relevant content knowledge support the effective allocation of intrinsic, extraneous, and germane cognitive load?

Introduction: Worked examples support initial skill acquisition. They often show skill application on content knowledge from another, "exemplifying" domain (e.g., argumentation skills have to be applied to some contents). Although learners' focus should remain on the skill, learners need to understand the content knowledge to benefit from worked examples. Previous studies relied on exemplifying domains that are familiar and contain simple topics, to keep learners' focus on skill acquisition. Aim: We examined whether using a relevant exemplifying domain would allow learners to acquire both skills and content knowledge simultaneously, or whether relevant content distracts from the main learning goal of skill acquisition. Methods and results: In a training study with 142 psychology students, we used example-based learning materials with an exemplifying domain that was either relevant or irrelevant for participants' course outcomes. We assessed cognitive load, declarative knowledge about skills and course-related content knowledge, and argumentation quality. Incorporating relevant content knowledge in worked examples did not reduce learning outcomes compared to a condition using an irrelevant exemplifying domain. Discussion: Contrary to previous research, the results suggest that worked examples with a relevant exemplifying domain could possibly be an efficient teaching method for fostering skills and content knowledge simultaneously.

Interrogating data-independent acquisition LC-MS/MS for affinity proteomics.

Data-Independent Acquisition (DIA) LC-MS/MS is an attractive partner for co-immunoprecipitation (co-IP) and affinity proteomics in general. Reducing the variability of quantitation by DIA could increase the statistical contrast for detecting specific interactors versus what has been achieved in Data-Dependent Acquisition (DDA). By interrogating affinity proteomes featuring both DDA and DIA experiments, we sought to evaluate the spectral libraries, the missingness of protein quantity tables, and the CV of protein quantities in six studies representing three different instrument manufacturers. We examined four contemporary bioinformatics workflows for DIA: FragPipe, DIA-NN, Spectronaut, and MaxQuant. We determined that (1) identifying spectral libraries directly from DIA experiments works well enough that separate DDA experiments do not produce larger spectral libraries when given equivalent instrument time; (2) experiments involving mock pull-downs or IgG controls may feature such indistinct signals that contemporary software will struggle to quantify them; (3) measured CV values were well controlled by Spectronaut and DIA-NN (and FragPipe, which implements DIA-NN for the quantitation step); and (4) when FragPipe builds spectral libraries and quantifies proteins from DIA experiments rather than performing both operations in DDA experiments, the DIA route results in a larger number of proteins quantified without missing values as well as lower CV for measured protein quantities. Supplementary Information: The online version contains supplementary material available at 10.1007/s42485-024-00166-4.

Symbiotic nitrogen fixation reduces belowground biomass carbon costs of nitrogen acquisition under low, but not high, nitrogen availability.

Many plant species form symbiotic associations with nitrogen-fixing bacteria. Through this symbiosis, plants allocate photosynthate belowground to the bacteria in exchange for nitrogen fixed from the atmosphere. This symbiosis forms an important link between carbon and nitrogen cycles in many ecosystems. However, the economics of this relationship under soil nitrogen availability gradients is not well understood, as plant investment toward symbiotic nitrogen fixation tends to decrease with increasing soil nitrogen availability. Here, we used a manipulation experiment to examine how costs of nitrogen acquisition vary under a factorial combination of soil nitrogen availability and inoculation with Bradyrhizobium japonicum in Glycine max L. (Merr.). We found that inoculation decreased belowground biomass carbon costs to acquire nitrogen and increased total leaf area and total biomass, but these patterns were only observed under low fertilization and were the result of increased plant nitrogen uptake and no change in belowground carbon allocation. These results suggest that symbioses with nitrogen-fixing bacteria reduce carbon costs of nitrogen acquisition by increasing plant nitrogen uptake, but only when soil nitrogen is low, allowing individuals to increase nitrogen allocation to structures that support aboveground growth. This pattern may help explain the prevalence of plants capable of forming these associations in less fertile soils and provides useful insight into understanding the role of nutrient acquisition strategy on plant nitrogen uptake across nitrogen availability gradients.

Idiosyncratic gesture use in a mother-infant dyad in chimpanzees (Pan troglodytes schweinfurthii) in the wild.

One promising method to tackle the question, "In which modality did language evolve?" is by studying the ontogenetic trajectory of signals in human's closest living relatives, including chimpanzees (Pan troglodytes). Concerning gestures, current debates centre on four different hypotheses: "phylogenetic ritualization", "social transmission through imitation", "ontogenetic ritualization", and "social negotiation". These differ in their predictions regarding idiosyncratic gestures, making such occurrences a crucial area of investigation. Here, we describe a novel and potential idiosyncratic behaviour - 'hand-on-eye' - which was initially observed in one mother-infant dyad in a community of chimpanzees living in the wild. We systematically investigated the form, sequential organisation, intentionality, usage, function, and distribution of the behaviour over a five-year period. The results showed that 'hand-on-eye' was nearly exclusively deployed in a single mother-infant dyad, was accompanied by hallmarks of intentionality, and served to initiate or resume joint dorsal travel. Although the behaviour was observed once in each of three other mother-infant dyads, these lacked the same frequency and hallmarks of intentionality. 'Hand-on-eye' thus qualifies as an idiosyncratic gesture. The proposed developmental pathway gives support to both the "ontogenetic ritualization" and "social negotiation" hypotheses. It also stresses the crucial need for longitudinal approaches to tackle developmental processes that are triggered by unique circumstances and unfold over relatively long time windows.

Evaluation of cucumber seed germination vigor under salt stress environment based on improved YOLOv8.

Seed germination vigor is one of the important indexes reflecting the quality of seeds, and the level of its germination vigor directly affects the crop yield. The traditional manual determination of seed germination vigor is inefficient, subjective, prone to damage the seed structure, cumbersome and with large errors. We carried out a cucumber seed germination experiment under salt stress based on the seed germination phenotype acquisition platform. We obtained image data of cucumber seed germination under salt stress conditions. On the basis of the YOLOv8-n model, the original loss function CIoU_Loss was replaced by ECIOU_Loss, and the Coordinate Attention(CA) mechanism was added to the head network, which helped the model locate and identify the target. The small-target detection head was added, which enhanced the detection accuracy of the tiny target. The precision P, recall R, and mAP of detection of the model improved from the original values of 91.6%, 85.4%, and 91.8% to 96.9%, 97.3%, and 98.9%, respectively. Based on the improved YOLOv8-ECS model, cucumber seeds under different concentrations of salt stress were detected by target detection, cucumber seed germination rate, germination index and other parameters were calculated, the root length of cucumber seeds during germination was extracted and analyzed, and the change characteristics of root length during cucumber seed germination were obtained, and finally the germination activity of cucumber seeds under different concentrations of salt stress was evaluated. This work provides a simple and efficient method for the selection and breeding of salt-tolerant varieties of cucumber.

Case Report: Contribution of [18F]FET PET in differential diagnosis between radionecrosis and progression in metastasis-reproducibility and superiority of dynamic acquisitions.

We present the case of a 67-year-old woman with metastatic invasive ductal carcinoma of the left breast, in whom a follow-up magnetic resonance imaging, 3 months after encephalic radiotherapy, revealed a significant increase in the size of two brain metastases, potentially indicating progressive disease within the radiation field. Subsequent [18F] fluorodeoxyglucose ([18F]FDG) and [18F] fluoroethyl-L-tyrosine positron emission tomography ([18F]FET PET) scans were performed to distinguish radionecrosis from tumor progression. Despite a dynamic [18F]FET time-activity curve (TAC) against progression, the exceeding of the 1.9 cutoff by mean tumor to brain ratio (TBR) and interdisciplinary considerations led to the resection of one lesion. Histopathology revealed necrosis due to radiotherapy, without viable tumor proliferation. To verify radionecrosis, a second [18F]FET PET scan was conducted, showing consistent findings. In metastasis differentiation, the mean TBR cutoff of 1.9 and TAC analysis achieved a sensitivity of 95% and specificity of 91%. The discrepancy between the TAC and TBR emphasizes the need for consideration, and a time delay between radiotherapy and PET may impact TBR cutoffs. In addition, differences in radiosensitivity suggest a lower metastasis pre-test probability of progression, and it might be why a TAC analysis could be more effective in distinguishing true progression from treatment related changes in metastasis. This case demonstrates the accuracy of dynamic [18F]FET PET and suggests its utility for post-treatment metastasis evaluation, and further research on post-treatment delay could lead to improved performances of dynamic [18F]FET PET.

Modeling the impact of MRI acquisition bias on structural connectomes: Harmonizing structural connectomes.

One way to increase the statistical power and generalizability of neuroimaging studies is to collect data at multiple sites or merge multiple cohorts. However, this usually comes with site-related biases due to the heterogeneity of scanners and acquisition parameters, negatively impacting sensitivity. Brain structural connectomes are not an exception: Being derived from T1-weighted and diffusion-weighted magnetic resonance images, structural connectivity is impacted by differences in imaging protocol. Beyond minimizing acquisition parameter differences, removing bias with postprocessing is essential. In this work we create, from the exhaustive Human Connectome Project Young Adult dataset, a resampled dataset of different b-values and spatial resolutions, modeling a cohort scanned across multiple sites. After demonstrating the statistical impact of acquisition parameters on connectivity, we propose a linear regression with explicit modeling of b-value and spatial resolution, and validate its performance on separate datasets. We show that b-value and spatial resolution affect connectivity in different ways and that acquisition bias can be reduced using a linear regression informed by the acquisition parameters while retaining interindividual differences and hence boosting fingerprinting performance. We also demonstrate the generative potential of our model, and its generalization capability in an independent dataset reflective of typical acquisition practices in clinical settings.

One of the main roadblocks to using multisite neuroimaging data is the effect of acquisition bias due to the heterogeneity of acquisition parameters associated with various sites. This can negatively impact the sensitivity of machine learning models employed in neuroscience. Thus, it is extremely important to model the effect of this bias. In this work, we address this issue at the level of brain structural connectivity, an important biomarker for various brain disorders. We propose a simple linear regression model to minimize this effect using high-quality data from the Human Connectome Project, and show its generalizability to a clinical dataset.

Bounded risk disposition explains Turing patterns and tipping points during spatial contagions.

Spatial contagions, such as pandemics, opinion polarization, infodemics and civil unrest, exhibit non-trivial spatio-temporal patterns and dynamics driven by complex human behaviours and population mobility. Here, we propose a concise generic framework to model different contagion types within a suitably defined contagion vulnerability space. This space comprises risk disposition, considered in terms of bounded risk aversion and adaptive responsiveness and a generalized susceptibility acquisition. We show that resultant geospatial contagion configurations follow intricate Turing patterns observed in reaction-diffusion systems. Pattern formation is shown to be highly sensitive to changes in underlying vulnerability parameters. The identified critical regimes (tipping points) imply that slight changes in susceptibility acquisition and perceived local risks can significantly alter the population flow and resultant contagion patterns. We examine several case studies using Australian datasets (COVID-19 pandemic; crime incidence; conflict exposure during COVID-19 protests; real estate businesses and residential building approvals) and demonstrate that these spatial contagions generated Turing patterns in accordance with the proposed model.

Heme homeostasis and its regulation by hemoproteins in bacteria.

Heme is an important cofactor and a regulatory molecule involved in various physiological processes in virtually all living cellular organisms, and it can also serve as the primary iron source for many bacteria, particularly pathogens. However, excess heme is cytotoxic to cells. In order to meet physiological needs while preventing deleterious effects, bacteria have evolved sophisticated cellular mechanisms to maintain heme homeostasis. Recent advances in technologies have shaped our understanding of the molecular mechanisms that govern the biological processes crucial to heme homeostasis, including synthesis, acquisition, utilization, degradation, trafficking, and efflux, as well as their regulation. Central to these mechanisms is the regulation of the heme, by the heme, and for the heme. In this review, we present state-of-the-art findings covering the biochemical, physiological, and structural characterization of important, newly identified hemoproteins/systems involved in heme homeostasis.

The factors that influence the diagnostic accuracy and sample adequacy of EUS-guided tissue acquisition for the diagnosis of solid pancreatic lesions.

Background and Objectives: EUS-guided tissue acquisition (EUS-TA) is the preferred method to acquire pancreatic cancer (PC) tissues. The factors associated with false-negative outcomes and inadequate samples should be explored to gain an understanding of EUS-TA. Methods: The patients who underwent EUS-TA for suspected solid PC but whose results were false-negative were analyzed. The PC patients who underwent EUS-TA with true-positive results on the first day of every month during the study period were selected as the control group. The factors influencing diagnostic accuracy and sample adequacy were explored. Results: From November 2017 to January 2022, 184 patients were included in the false-negative group, and 175 patients were included in the control group. Multivariate logistic regression demonstrated that the recent acute pancreatitis [odds ratio (OR): 0.478, 95% confidence interval (CI): 0.250-0.914, P = 0.026] and high echo component within the tumor (OR: 0.103, 95% CI: 0.027-0.400, P = 0.001) were independently associated with false-negative EUS-TA results. Meanwhile, using fine-needle biopsy (FNB) needles (OR: 2.270, 95% CI: 1.277-4.035, P = 0.005), more needle passes (OR: 1.651,95% CI: 1.239-2.199, P = 0.005), large tumor size (OR: 1.053, 95% CI: 1.029-1.077, P < 0.001), and high CA-19-9 level (OR: 1.001, 95% CI: 1.000-1.001, P = 0.019) were independently associated with true-positive EUS-TA outcomes. Three needle passes are needed to achieve optimal EUS-TA outcomes. Tumor location in the body/tail (OR: 1.38, 95% CI: 1.01-1.72; P = 0.04), needle passes ≥3 (OR: 1.90; 95% CI: 1.22-2.56; P < 0.001), and using the FNB needle (OR: 2.10; 95%: 1.48-2.85; P < 0.001) were independently related to sample adequacy. Conclusion: Numerous factors were identified to be associated with the diagnostic accuracy and sample adequacy of EUS-TA.

Longitudinal trajectories of the neural encoding mechanisms of speech-sound features during the first year of life.

Infants quickly recognize the sounds of their mother language, perceiving the spectrotemporal acoustic features of speech. However, the underlying neural machinery remains unclear. We used an auditory evoked potential termed frequency-following response (FFR) to unravel the neural encoding maturation for two speech sound characteristics: voice pitch and temporal fine structure. 37 healthy-term neonates were tested at birth and retested at the ages of six and twelve months. Results revealed a reduction in neural phase-locking onset to the stimulus envelope from birth to six months, stabilizing by twelve months. While neural encoding of voice pitch remained consistent across ages, temporal fine structure encoding matured rapidly from birth to six months, without further improvement from six to twelve months. Results highlight the critical importance of the first six months of life in the maturation of neural encoding mechanisms that are crucial for phoneme discrimination during early language acquisition.