Urinary haloacetic acid concentrations in relation to sex and thyroid hormones among reproductive-aged men.

Sex and thyroid hormones are critical for male reproductive health. However, the associations between haloacetic acid (HAA) exposure - a known endocrine disruptor - and sex and thyroid hormones in humans remains unclear. We thus recruited 502 male participants seeking fertility evaluation from a reproductive center. We measured concentrations of sex and thyroid hormones in a single blood sample and dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) in repeated urine samples. Multivariable linear regression models were constructed to evaluate the associations between HAA concentrations and hormone measurements. After adjusting for potential confounders and urinary creatinine concentrations, urinary concentrations of TCAA were inversely associated with serum levels of sex hormone-binding globulin (SHBG), testosterone (T), T/luteinizing hormone ratio (T/LH), and thyroid stimulating hormone (TSH) (all P for trend < 0.10). Compared with participants in the lowest quartile of TCAA concentrations, those in the highest quartile had reduced serum levels of SHGB by 14.2 % (95% CI: -26.7, -3.0 %), T by 11.1 % (95% CI: -21.7, -1.3 %), T/LH by 21.0 % (95% CI: -36.7, -7.1 %), and TSH by 19.1 % (95% CI: -39.7, -1.5 %). Additionally, we observed inverse associations between continuous measurements of urinary HAAs and serum levels of free T, bioactive T, and estradiol. Our findings suggest that male HAA exposure may be associated with disrupted sex and thyroid function.

Analysis of volatiles from the thermal decomposition of Amadori rearrangement products in the cysteine-glucose Maillard reaction and density functional theory study.

The Amadori rearrangement products are an important flavor precursor in the Maillard reaction. Its thermal decomposition products usually contribute good flavors in foods. Therefore, investigating the thermal breakdown of Amadori products is significant for understanding the flavor forming mechanism in the Maillard reaction. In this study, volatiles from thermal decomposition of Amadori products in cysteine and glucose Maillard reaction was investigated by a thermal desorption cryo-trapping system combined with gas chromatography-mass spectrometry (GC-MS). A total of 60 volatiles were detected and identified. Meanwhile, the forming mechanism of 2-methylthiophene, a major decomposition product, was also investigated by using density functional theory. Seventeen reactions, 12 transition states, energy barrier and rate constant of each reaction were finally obtained. Results reveal that it is more likely for Amadori products of cysteine and glucose to undergo decomposition under neutral or weakly alkaline conditions.

A fluorescence probe with targeted mitochondria for detecting hydrogen peroxide in vitro and in diabetic mice.

We designed and prepared probe W-1 for the detection of H2O2. W-1 showed excellent selectivity for H2O2 and was accompanied by colorimetric signal changes. The excellent linear relationship between fluorescence intensity and H2O2 concentration (0-100 µM) provided favorable conditions for its quantitative detection. In addition, the combination of portable test strips with a smartphone platform provided great convenience for on-site visual detection of H2O2. Moreover, W-1 possessed targeting mitochondria property and could be applied to image the exogenous and endogenous H2O2 in cells to distinguish normal cells and cancer cells. Lastly, W-1 was used for monitoring the H2O2 fluctuation of the diabetic process in mice, and the results showed an increase in H2O2 levels in diabetes. Therefore, the probe provided a tool for understanding the pathological and physiological mechanisms of diabetes by imaging H2O2.

Single immunization of non-adjuvanted recombinant TTFC-mi3 nanoparticle vaccine elicited a rapid and potent protective immunity against tetanus.

The conventional inactivated tetanus toxin plays an instrumental role in preventing tetanus. Nevertheless, the challenges associated with its production process, the potential for adverse reactions, and reduced effectiveness in vulnerable populations such as neonates and the elderly rise the need for a novel tetanus toxin vaccine. Recombinant subunit vaccine offer a viable solution, and the tetanus toxin fragment C (TTFC) is emerging as a promising candidate. In this study, through spontaneous isopeptide bond formation we conjugated the recombinant TTFC to self-assembled mi3 nanoparticle, which derived from an optimized KDPG aldolase, and generated the TTFC-mi3 protein nanoparticle vaccine. We found that TTFC-mi3 is stable, uniform spherical nanoparticles. Comparing with the free TTFC alone, TTFC-mi3 enhances the uptake and subsequent activation of dendric cells (DCs). In addition, a single dose of adjuvant-free TTFC-mi3 elicited a more rapid and potent protective immunity in mice. Moreover, TTFC-mi3 is of favorable safety in vitro and in vivo. Our findings indicate that TTFC-mi3 is a rapid-response, non-aluminum-adjuvanted vaccine against tetanus.

Deep Learning Models of Multi-Scale Lesion Perception Attention Networks for Diagnosis and Staging of Pneumoconiosis: A Comparative Study with Radiologists.

Accurate prediction of pneumoconiosis is essential for individualized early prevention and treatment. However, the different manifestations and high heterogeneity among radiologists make it difficult to diagnose and stage pneumoconiosis accurately. Here, based on DR images collected from two centers, a novel deep learning model, namely Multi-scale Lesion-aware Attention Networks (MLANet), is proposed for diagnosis of pneumoconiosis, staging of pneumoconiosis, and screening of stage I pneumoconiosis. A series of indicators including area under the receiver operating characteristic curve, accuracy, recall, precision, and F1 score were used to comprehensively evaluate the performance of the model. The results show that the MLANet model can effectively improve the consistency and efficiency of pneumoconiosis diagnosis. The accuracy of the MLANet model for pneumoconiosis diagnosis on the internal test set, external validation set, and prospective test set reached 97.87%, 98.03%, and 95.40%, respectively, which was close to the level of qualified radiologists. Moreover, the model can effectively screen stage I pneumoconiosis with an accuracy of 97.16%, a recall of 98.25, a precision of 93.42%, and an F1 score of 95.59%, respectively. The built model performs better than the other four classification models. It is expected to be applied in clinical work to realize the automated diagnosis of pneumoconiosis digital chest radiographs, which is of great significance for individualized early prevention and treatment.

Experience from transport teams on interhospital transfer of patients with extracorporeal membrane oxygenation support: A qualitative study.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) can be a life-saving treatment for patients requiring advanced cardiopulmonary support. Several ECMO centres offer interhospital transport (ECMO IHT) services that involve establishing ECMO teams to initiate ECMO at referring hospitals and then transfer patients to ECMO centres. ECMO IHT is often high risk and complex. Understanding the experience of transport team members is crucial to ensure patient safety and promote quality improvement. AIM: To explore the experiences of transport teams performing ECMO IHT. STUDY DESIGN: A descriptive qualitative methodology was adopted. RESULTS: Thirteen health care professionals who have performed ECMO IHT at a general hospital in China agreed to be interviewed and enrolled in this study. Two investigators conducted face-to-face individual interviews in September-November 2022. All interviews were audio-recorded, transcribed verbatim and analysed using inductive thematic analysis. Three main themes and nine sub-themes were developed: (1) practicing with good organizational management (conducting training programs, cultivating the spirit of good teamwork and developing a standardized transport procedure), (2) dedicated to ensuring patient safety (adequate preparation and regular checking to reduce risk, accurate evaluation to avoid futility and maintaining communication to increase safety) and (3) having confidence despite being uneasy (feeling stressed is common, facing insecurity in transport settings and gaining confidence through practice). CONCLUSIONS: Health care professionals must adequately prepare and assess ECMO IHT to ensure patient safety. Supportive measures should be taken to ensure team members' health and improve patient safety. Good communication and teamwork could improve this challenging task. Further research is required for training programs and establishing standardized transport procedures. RELEVANCE TO CLINICAL PRACTICE: This study presents multi-professional perspectives on the experience of performing ECMO IHT to help management identify what needs to be further developed. With the increasing number of ECMO IHT, promoting its standardization is warranted.

Direct Synthesis of C4-Acyl Indoles via C-H Acylation.

The direct synthesis of C4-acyl indoles deprived of C2 and C3 substituents has proven to be challenging, with scarce efficient synthetic routes being reported. Herein, we disclose a highly site-selective palladium-catalyzed C-H acylation for the construction of C4-acyl indoles via a Catellani-Lautens cyclization strategy. In addition, we systematically studied the ortho C-H acylation mechanism of iodoaniline through density functional theory (DFT) calculations and combined experimental results to elucidate the principle of high chemoselectivity brought by triazine benzoate as an acylation reagent.

Hypoglobus, Exophthalmos, and Interpupillary Distance: Measuring Globe Dystopia in Thyroid Eye Disease.

PURPOSE: Thyroid eye disease (TED) is characterized by a variety of disfiguring periocular changes. Vertical globe changes affecting the relative position of the eyelids are not well understood in patients with TED. This study seeks to determine the effect of orbital decompression on vertical globe displacement in patients with TED, without TED, and with intraconal tumor (ICT). METHODS: For this cross-sectional study, a clinical database was used to identify patients with TED. Comparison groups were drawn from separate anonymized databases. Vertical position and interpupillary distance (IPD) were measured from photographs and exophthalmos was measured via Hertel's exophthalmometer. Primary outcomes were vertical globe position at baseline and postoperatively in patients with TED and ICT. Secondary outcomes included the relationship between vertical globe position, exophthalmos, and IPD. RESULTS: Among 269 participants meeting the inclusion criteria, mean vertical globe position was significantly lower in patients with TED following lateral decompression surgery compared to controls, after accounting for race, age, and sex. While patients with ICT had a significant difference in preoperative and postoperative IPD, patients with TED did not. Medial or inferior decompression did not significantly change globe position and lateral decompression did not cause lateral canthal dystopia in patients with TED. No association between postoperative changes in exophthalmometry, IPD, and globe position was found in patients with TED. CONCLUSIONS: Patients with TED experience hypoglobus that does not improve following decompression surgery. There was no correlation between change in vertical globe position and exophthalmos or IPD among patients with TED. Surgeons should discuss the possibility of hypoglobus as a persistent finding for patients with TED undergoing decompression surgery.

The environmental risk threshold (HC5) for Cd remediation in Chinese agricultural soils.

Given the increasing concern over Cd contamination of agricultural soils in China, reducing the availability of the toxic metal has become an important remedial strategy. However, the lack of a unified evaluation framework complicates the assessment of remediation efficiency of different practices. Here, we evaluated the general extraction method (GEM) of available Cd in nine typical soil types by comparing extraction agents, including CaCl2, EDTA, Mehlich-Ⅲ, HCl and DTPA. The safe grain concentration of different agricultural products from National Food Safety Standards Limits of Contaminants in Food (GB 2762-2022) was then applied to understand soil limited available Cd concentration based on dose-response curves. We also derived environmental risk threshold (HC5) values for Cd remediation in agricultural soils by constructing species sensitivity distribution (SSD) curves. The results showed that Mehlich-Ⅲ best predicted Cd accumulation in crops (with 76.5% of explanation of grain Cd) and was selected as the GEM of soil available Cd for subsequent analyses. The regression coefficient (R2) of dose-response curves fitting between Cd absorption in crop tissues and soil available Cd extracted by GEM based on 30 different crop species varied from 51.0% to 79.5%, and the derived limit concentration of soil available Cd based on standard GB 2762-2022 was 0.18-0.76 mg‧kg-1. An HC5 of 0.19 mg‧kg-1 was then calculated, meaning that a concentration of available Cd in agricultural soil below 0.19 mg‧kg-1 ensures that 95% of agricultural products meet the quality and safety requirements of standard GB 2762-2022. The prediction model was well verified in the field test, indicating that can correctly estimate the soil available Cd based on the content of Cd in plant. This study provides a robust scientific framework for deriving the risk threshold for Cd remediation in agricultural soils and could be quite useful for establishing soil remediation standards.

Myricetin inhibits 4 T1 breast tumor growth in mice via induction of Nrf-2/GPX4 pathway-mediated Ferroptosis.

Ferroptosis is a recently identified form of programmed cell death that is iron-dependent and closely involved in the pathogenesis of breast cancer. Past studies have identified myricetin as being able to inhibit breast cancer growth through its targeting of apoptotic mechanisms, but the precise mechanisms whereby it exerts its antitumoral effects in breast cancer remain to be characterized in detail. Here, the effects of myricetin on the induction of ferroptosis in breast cancer cells were investigated. It was found that myricetin was able to significantly inhibit 4 T1 tumor cell viability and colony forming activity, increasing the level of MDA, Fe2+, and ROS within these cells. From a mechanistic perspective, myricetin was found to induce ferroptotic 4 T1 cell death via downregulating Nrf-2 and GPX4. In vivo experimentation demonstrated that myricetin treatment was sufficient to reduce the growth of subcutaneous breast tumors in female mice as evidenced by decreases in tumor weight and volume, while significantly inhibiting Nrf-2 and GPX4 expression within the tumors of treated mice. Myricetin is capable of readily suppressing breast tumor growth in mice via the induction of ferroptotic activity through the Nrf-2/GPX4 pathway. Myricetin may thus offer utility as a therapeutic agent for the management of breast cancer in clinical settings.

The effects of residential segregation on cognition among U.S. older adults: a systematic review based on the social determinants of health model.

OBJECTIVES: This systematic review aims to advance the understanding of the complicated effects of segregation on older adults' cognition and provide guidance for future research. METHOD: A systematic review using the Social Determinants of Health framework to examine the relationship between segregation and cognition across the selected literature. RESULTS: Eight papers met the criteria for inclusion. All selected studies examined the influence of living in a segregated area on older adults' cognition, covering older adults from different racial/ethnic groups. The association between segregation and cognition was found in different directions across different racial/ethnic groups. The effects can be varied depending on race/ethnicity, level of education, neighborhood socioeconomic status, or social context. CONCLUSION: This review identified existing gaps in understanding the relationship between segregation and cognition. Future studies should carefully adopt the segregation measures, acknowledge the varying segregation experience among different racial/ethnic groups, and consider more social determinant factors in research.

Switching from eltrombopag to hetrombopag in patients with primary immune thrombocytopenia: a post-hoc analysis of a multicenter, randomized phase III trial.

While studies have explored the feasibility of switching between various thrombopoietin receptor agonists in treating immune thrombocytopenia (ITP), data on the switching from eltrombopag to hetrombopag remains scarce. This post-hoc analysis of a phase III hetrombopag trial aimed to assess the outcomes of ITP patients who switched from eltrombopag to hetrombopag. In the original phase III trial, patients initially randomized to the placebo group were switched to eltrombopag. Those who completed this 14-week eltrombopag were eligible to switch to a 24-week hetrombopag. Treatment response, defined as a platelet count of ≥ 50 × 109/L, and safety were evaluated before and after the switch. Sixty-three patients who completed the 14-week eltrombopag and switched to hetrombopag were included in this post-hoc analysis. Response rates before and after the switch were 66.7% and 88.9%, respectively. Among those with pre-switching platelet counts below 30 × 109/L, eight out of 12 patients (66.7%) responded, while eight out of nine patients (88.9%) with pre-switching platelet counts between 30 × 109/L and 50 × 109/L responded post-switching. Treatment-related adverse events were observed in 50.8% of patients during eltrombopag treatment and 38.1% during hetrombopag treatment. No severe adverse events were noted during hetrombopag treatment. Switching from eltrombopag to hetrombopag in ITP management appears to be effective and well-tolerated. Notably, hetrombopag yielded high response rates, even among patients who had previously shown limited response to eltrombopag. However, these observations need to be confirmed in future trials.

Microfluidic Electrochemical Integrated Sensor for Efficient and Sensitive Detection of Candida albicans.

Traditional methods for the detection of pathogenic bacteria are time-consuming, less efficient, and sensitive, which affects infection control and bungles illness. Therefore, developing a method to remedy these problems is very important in the clinic to diagnose the pathogenic diseases and guide the rational use of antibiotics. Here, microfluidic electrochemical integrated sensor (MEIS) has been investigated, functionally for rapid, efficient separation and sensitive detection of pathogenic bacteria. Three-dimensional macroporous PDMS and Au nanotube-based electrode are successfully assembled into the modeling microchip, playing the functions of "3D chaotic flow separator" and "electrochemical detector," respectively. The 3D chaotic flow separator enhances the turbulence of the fluid, achieving an excellent bacteria capture efficiency. Meanwhile, the electrochemical detector provides a quantitative signal through enzyme-linked immunoelectrochemistry with improved sensitivity. The microfluidic electrochemical integrated sensor could successfully isolate Candida albicans (C. albicans) in the range of 30-3,000,000 CFU in the saliva matrix with over 95% capture efficiency and sensitively detect C. albicans in 1 h in oral saliva samples. The integrated device demonstrates great potential in the diagnosis of oral candidiasis and is also applicable in the detection of other pathogenic bacteria.

High resolution assessment of commercial fisheries activity along the US West Coast using Vessel Monitoring System data with a case study using California groundfish fisheries.

Commercial fisheries along the US West Coast are important components of local and regional economies. They use various fishing gear, target a high diversity of species, and are highly spatially heterogeneous, making it challenging to generate a synoptic picture of fisheries activity in the region. Still, understanding the spatial and temporal dynamics of US West Coast fisheries is critical to meet the US legal mandate to manage fisheries sustainably and to better coordinate activities among a growing number of users of ocean space, including offshore renewable energy, aquaculture, shipping, and interactions with habitats and key non-fishery species such as seabirds and marine mammals. We analyzed vessel tracking data from Vessel Monitoring System (VMS) from 2010 to 2017 to generate high-resolution spatio-temporal estimates of contemporary fishing effort across a wide range of commercial fisheries along the entire US West Coast. We identified over 247,000 fishing trips across the entire VMS data, covering over 25 different fisheries. We validated the spatial accuracy of our analyses using independent estimates of spatial groundfish fisheries effort generated through the NOAA's National Marine Fisheries Service Observer Program. Additionally, for commercial groundfish fisheries operating in federal waters in California, we combined the VMS data with landings and ex-vessel value data from California commercial fisheries landings receipts to generate highly resolved estimates of landings and ex-vessel value, matching over 38,000 fish tickets with VMS data that included 87% of the landings and 76% of the ex-vessel value for groundfish. We highlight fisheries-specific and spatially-resolved patterns of effort, landings, and ex-vessel value, a bimodal distribution of fishing effort with respect to depth, and variable and generally declining effort over eight years. The information generated by our study can help inform future sustainable spatial fisheries management and other activities in the marine environment including offshore renewable energy planning.

Role of clinical and multidetector computed tomography (MDCT) features in the prediction of patients with intestinal lipoma developing intussusception.

Background: Intestinal lipoma is considered the most common benign tumor that causes intussusception. This retrospective case-control study aimed to present the clinical and multidetector computed tomography (MDCT) features between intestinal lipomas with and without intussusception and examine risk factors that predict intussusception caused by intestinal lipomas. Methods: We retrospectively analyzed 281 adult patients diagnosed with intestinal lipoma by radiologists using whole-abdominal MDCT between January 2015 and August 2022. Patients were divided into adult intussusception (AI) and non-AI groups based on MDCT images. Univariate logistic regression was performed to identify risk factors for intestinal lipoma-induced intussusception. Results: A total of 281 patients with intestinal lipomas were included in the study, with an average age of 68.0±11.3 years, and the male to female ratio was about 1:1.4. Among them, 24 patients developed lipoma-induced intussusception. Patients in the AI group presented with more abdominal pain (70.8% vs. 47.1%, P=0.03), nausea/vomiting (37.5% vs. 14.8%, P=0.009), hematochezia/melena (29.2% vs. 11.3%, P=0.02), and abdominal tenderness (66.7% vs. 24.9%, P<0.001). Lipomas were more common in the small bowel (224/281, 79.7%) than the large bowel (57/281, 20.3%). Lipomas in the AI group showed more heterogeneous hypodensity (41.7% vs. 15.6%, P=0.004), longer length (median, 2.2 vs. 1.2 cm, P<0.001), and larger volume (median, 4.1 vs. 0.6 cm3, P<0.001). In the univariate logistic regression, lipoma density [odds ratio (OR) =3.875, 95% confidence interval (CI): 1.609-9.331, P=0.003] and lipoma length (OR =3.216, 95% CI: 1.977-5.231, P<0.001) were risk factors for intestinal lipoma-induced intussusception. Conclusions: More patients in the AI group have digestive tract symptoms than those in the non-AI group. Lipoma density and length are risk factors for intussusception in patients with intestinal lipoma. In addition, the common site of intestinal lipoma may have changed from the colon to the small intestine.

For older women, the majority of hip fragility fractures and radiographic vertebral fragility fractures occur among the densitometrically osteoporotic population: a literature analysis.

It has been frequently cited that 'the majority of fragility fractures (FF) occur at non-osteoporotic bone mineral density (BMD)'. For the reports with T-score measured around the time of a hip fracture, we conducted a systematic literature search in December 2022, and resulted in 10 studies with five for Caucasian women and five for East Asian women. Femoral neck (FN) T-score was reported in five Caucasian studies and three East Asian studies, three of five Caucasian studies had a mean T-score ≤-2.5, and one study had the majority of their patients measuring a mean T-score ≤-2.5. All three East Asian studies reported a mean FN T-score ≤-2.7. Total hip T-score was reported in two Caucasian studies and three East Asian studies, the two Caucasian studies both had a mean T-score ≤-2.5, and all three East Asian studies had a mean T-score ≤-2.6. A new literature search conducted in April 2024 results in additional three studies, with results being consistent with the data described above. A trend was noted that 'younger' patients suffer from hip fractures at a 'higher' T-score. For the highly cited articles where the notion the majority of FF occur at non-osteoporotic BMD was derived from, authors reported prospective epidemiological studies where BMD was not measured at the timepoint of hip fracture, instead, BMD was measured at the study baseline. These epidemiological studies suggest that >50% of hip fractures likely occur in women with an osteoporotic FN or hip T-score. However, a pattern was seen that older men suffer from hip fracture at a notably higher T-score than older women. For the cases of radiographic vertebral FF, despite varying criteria being used to classify these FFs, the majority of female patients had spine densitometric osteoporosis. Literature shows, compared with the cases of hip fracture, distal forearm fracture occurs at a 'younger' age and 'higher' BMD, suggesting distal forearm fracture is more likely associated with a 'higher' trauma energy level.

Ferroptosis and hepatocellular carcinoma: the emerging role of lncRNAs.

Hepatocellular carcinoma is the most common form of primary liver cancer and poses a significant challenge to the medical community because of its high mortality rate. In recent years, ferroptosis, a unique form of cell death, has garnered widespread attention. Ferroptosis, which is characterized by iron-dependent lipid peroxidation and mitochondrial alterations, is closely associated with the pathological processes of various diseases, including hepatocellular carcinoma. Long non-coding RNAs (lncRNAs), are a type of functional RNA, and play crucial regulatory roles in a variety of biological processes. In this manuscript, we review the regulatory roles of lncRNAs in the key aspects of ferroptosis, and summarize the research progress on ferroptosis-related lncRNAs in hepatocellular carcinoma.

Septal stimulation attenuates hippocampal seizure with subregion specificity.

OBJECTIVE: Deep brain stimulation (DBS) is a promising approach for the treatment of epilepsy. However, the optimal target for DBS and underlying mechanisms are still not clear. Here, we compared the therapeutic effects of DBS on distinct septal subregions, aimed to find the precise targets of septal DBS and related mechanisms for the clinical treatment. METHODS: Assisted by behavioral test, electroencephalography (EEG) recording and analyzing, selectively neuronal manipulation and immunohistochemistry, we assessed the effects of DBS on the three septal subregions in kainic acid (KA)-induced mouse seizure model. RESULTS: DBS in the medial septum (MS) not only delayed generalized seizure (GS) development, but reduced the severity; DBS in the vertical diagonal band of Broca (VDB) only reduced the severity of GS, while DBS in the horizontal diagonal band of Broca (HDB) subregion showed no anti-seizure effect. Notably, DBS in the MS much more efficiently decreased abnormal activation of hippocampal neurons. EEG spectrum analysis indicated that DBS in the MS and VDB subregions mainly increased the basal hippocampal low-frequency (delta and theta) rhythm. Furthermore, ablation of cholinergic neurons in the MS and VDB subregions blocked the anti-seizure and EEG-modulating effects of septal DBS, suggesting the seizure-alleviating effect of DBS was dependent on local cholinergic neurons. SIGNIFICANCE: DBS in the MS and VDB, rather than HDB, attenuates hippocampal seizure by activation of cholinergic neurons-augmented hippocampal delta/theta rhythm. This may be of great therapeutic significance for the clinical treatment of epilepsy with septal DBS. PLAIN LANGUAGE SUMMARY: The optical target of deep brain stimulation in the septum is still not clear. This study demonstrated that stimulation in the medial septum and vertical diagonal band of Broca subregions, but not the horizontal diagonal band of Broca, could alleviate hippocampal seizure through cholinergic neurons-augmented hippocampal delta/theta rhythm. This study may shed light on the importance of precise regulation of deep brain stimulation therapy in treating epileptic seizures.