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Xiang Li,1 Mengtian Pan,1 Xinjuan Tian,1 Lele Zixin Yang,2 Jingjing Zhang,1 Dongmei Yan,3 Baohui Xu,4 Li Zhao,1 Weirong Fang1 1Department of Physiology, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, People’s Republic of China; 2The Pennsylvania State University, Eberly College of Science, State College, PA, USA; 3Department of Immunology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin, People’s Republic of China; 4Department of Surgery, Stanford University School of Medicine, Stanford, CA, USACorrespondence: Li Zhao; Weirong Fang, Email zhaoli@cpu.edu.cn; weirongfang@cpu.edu.cnBackground: Tripartite motif containing 59 (TRIM59) is a ubiquitin ligase and is involved in the pathogenesis of various diseases, including cancers, sepsis, and other immune-related diseases. However, it has not been defined whether TRIM59 plays a role in ischemic stroke in mice.Methods: This study determined the influence of Trim59 deficiency on experimental stroke outcomes and the cerebral proteomic profile using myeloid cell Trim59 conditional knockout (Trim59-cKO) mice and a label-free quantitative proteomic profiling technique. The possible mechanisms by which TRIM59 affected stroke onset were elucidated by in vivo and in vitro experiments.Results: Immunofluorescence staining results showed that TRIM59 expression was up-regulated after cerebral ischemia and co-localized with macrophages. Myeloid cell Trim59 deficiency exacerbated ischemic injury on day 3 after experimental stroke. In proteomic analysis, 23 differentially expressed proteins were identified in ischemic brain of Trim59-cKO mice as compared to Trim59flox/flox mice. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the differentially expressed proteins were enriched in complement and coagulation cascades. Protein–protein interaction analysis suggested the central role of clusterin in the interaction network. ELISA and Western blot assays confirmed the reduced levels of clusterin protein in the ischemic brains of Trim59-cKO mice. Further experimental results showed that clusterin was expressed in neurons. Conditional co-culture experiments of primary neurons and bone marrow-derived macrophages demonstrated that LPS stimulated macrophages to secrete complement C3. In addition, TRIM59 may affect the changes in clusterin expression in an indirect manner by influencing the secretion of complement C3 in macrophages. In vivo experiments also proved a significant increase in C3 levels in the brains of Trim59-cKO mice after ischemia.Conclusion: Myeloid cell Trim59 deficiency aggravated ischemic stroke outcomes in conjunction with a distinct cerebral proteomic profile, and the underlying mechanism may be related to the regulation of macrophage C3 expression by TRIM59.Keywords: Trim59, ischemic stroke, proteomic profile, complement and coagulation cascades, C3

Jie-Ying Wan, Li-Zhen Yang Division of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, People’s Republic of ChinaCorrespondence: Li-Zhen Yang, Tel +86-15618690375, Email dryanginsh@sina.comPurpose: The correlation between liver enzymes and blood glucose in diabetes mellitus remains unclear. The purpose of present three-year retrospective study was to explore the association between liver enzymes and glycemia in type 2 diabetes mellitus (T2DM).Patients and Methods: 2046 participants (non-fatty liver, n=1253; fatty liver, n=793) with T2DM were included in our study. For all these patients, related basic clinical information, biochemical parameters and liver ultrasonic data were collected. The effects of liver enzymes on blood glucose levels were analysed by linear and binary logistic regression models.Results: In the comparative analyses between groups, gamma-glutamyltransferase (GGT) and serum alkaline phosphatase (AKP) levels increased with glycosylated haemoglobin A1c (HbA1c) concentration, but alanine aminotransferase and aspartate aminotransferase did not show the same trend. Adjusted for possible confounding factors, the linear regression models indicated the strong positive correlations between Log10 AKP, Log10 GGT and three blood glucose parameters (fasting glucose, postprandial glucose, and HbA1c) (all P< 0.01). And such correlations were more significant in the subgroups of fatty liver. Multivariate binary logistic regression showed that the ORs increased by 1.01 times higher per Log10 AKP unit in the highest blood glucose tertile (P< 0.01).Conclusion: GGT and especially AKP can aggravate hyperglycemia in T2DM patients, which provides new clues for the research and treatment of T2DM.Keywords: liver enzymes, fasting blood glucose, postprandial blood glucose, HbA1c, T2DM

The networks observed in the brain during resting-state activity are not entirely "task-free." Instead, they hint at a hierarchical structure prepared for adaptive cognitive functions. Recent studies have increasingly demonstrated the potential of resting-state fMRI to predict local activations or global connectomes during task performance. However, uncertainties remain regarding the unique and shared task-specific components within resting-state brain networks, elucidating local activations and global connectome patterns. A coherent framework is also required to integrate these task-specific components to predict local activations and global connectome patterns. In this work, we introduce the Rest2Task model based on the partial least squares-based multivariate regression algorithm, which effectively integrates mappings from resting-state connectivity to local activations and global connectome patterns. By analyzing the coefficients of the regression model, we extracted task-specific resting-state components corresponding to brain local activation or global connectome of various tasks and applied them to the brain lateralization prediction and psychiatric disorders diagnostic. Our model effectively substitutes traditional whole-brain functional connectivity (FC) in predicting functional lateralization and diagnosing brain disorders. Our research represents the inaugural effort to quantify the contribution of patterns (components) within resting-state FC to different tasks, endowing these components with specific task-related contextual information. The task-specific resting-state components offer new insights into brain lateralization processing and disease diagnosis, potentially providing fresh perspectives on the adaptive transformation of brain networks in response to tasks., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Single-element polarization in low dimensions is fascinating for constructing next-generation nanoelectronics with multiple functionalities, yet remains difficult to access with satisfactory performance. Here, spectroscopic evidences are presented for the spontaneous electronic polarization in tellurium (Te) films thinned down to bilayer, characterized by low-temperature scanning tunneling microscopy/spectroscopy. The unique chiral structure and centrosymmetry-breaking character in 2D Te gives rise to sizable in-plane polarization with accumulated charges, which is demonstrated by the reversed band-bending trends at opposite polarization edges in spatially resolved spectra and conductance mappings. The polarity of charges exhibits intriguing influence on imaging the moiré superlattice at the Te-graphene interface. Moreover, the plain spontaneous polarization robustly exists for various film thicknesses, and can universally preserve against different epitaxial substrates. The experimental validations of considerable electronic polarization in Te multilayers thus provide a realistic platform for promisingly facilitating reliable applications in microelectronic devices., (© 2024 Wiley‐VCH GmbH.)

Background: Syphilis coinfection among pregnant people living with HIV (PLH) may worsen pregnancy outcomes. We evaluated the impact of syphilis coinfection on pregnancies in south Brazil., Methods: Data were extracted from hospital records between January 1, 2008, and December 31, 2018. Preterm birth (PTB), low birth weight (LBW <2500 g), and a composite adverse infant outcome (AIO: HIV vertical transmission, loss to follow-up before HIV diagnosis, stillbirth, congenital syphilis) were evaluated among pregnancies without HIV and syphilis (PWOH + S), PLH monoinfection, syphilis monoinfection (PLS), and PLH with syphilis (PLH + S)., Results: Among 48,685 deliveries where patients were tested for HIV and syphilis, 1353 (2.8%) occurred in PLH; of these, 181 (13.4%) were HIV/syphilis coinfected (PLH + S). Among PLH, 2.4% of infants acquired HIV and 13.1% were lost to follow-up before HIV diagnosis. Among all PLS, 70.5% of infants acquired congenital syphilis. Across the cohort, 1.2% stillbirths/neonatal deaths occurred. Thirty-seven percent of PLH + S did not initiate antiretroviral therapy versus 15.4% of PLH monoinfection ( P < 0.001). Less than half (37.6%) of PLH + S had VDRL titers ≥1:16 compared with 21.7% of PLS only ( P < 0.001). Among PLH, syphilis coinfection and unknown/high VDRL titers (≥1:16) increased AIO risk more (adjusted relative risk [aRR], 3.96; 95% confidence interval [CI], 3.33-4.70) compared with low VDRL titers (≤1:8; aRR, 3.51; 95% CI, 2.90-4.25). Unsuppressed viremia (≥50 copies/mL) was associated with risk of PTB (aRR, 1.43; 95% CI, 1.07-1.92) and AIO (aRR, 1.38; 95% CI, 1.11-1.70) but not LBW. Lack of prenatal care was significant in predicting PTB and LBW in all PLH and PLS monoinfection., Conclusions: Syphilis coinfection worsens AIOs in all women and compounds negative effects of HIV infection during pregnancy. Effective syphilis treatment and HIV viral load suppression are paramount for optimal obstetric care., Competing Interests: Conflict of Interest and Sources of Funding: The authors have no competing interests or conflicts to declare., (Copyright © 2024 American Sexually Transmitted Diseases Association. All rights reserved.)

Long-term exposure to ultraviolet (UV) radiation induces skin photoaging, which manifests as oxidative stress, inflammation, and collagen degradation. Multiple approaches (topical or systemic retinoids, antioxidants, alpha-hydroxy acids, laser, surgery) are used in the treatment of photoaged skin, and the use of topical retinoids is currently a primary clinical treatment. Previous studies revealed that retinoic acid promotes keratinocyte proliferation and reduces melanin deposition and matrix metalloproteinase (MMP) secretion; it also causes potential allergic and inflammatory damage to the skin. This study aimed to investigate the therapeutic effects and mechanisms of trifarotene, a functional retinoic acid analog, on UV-irradiated photoaging ICR and BALB/c nude mice and UVB photodamaged human epidermal keratinocyte (HaCaT) cells by examining indicators such as collagen, oxidoreductase, and inflammatory factor presence through histochemical staining, Western blot, and ELISA. Results suggested that trifarotene significantly reduced UV-induced photoaging in mouse skin tissue, potentially by reducing oxidative stress damage and inflammatory factor release, and inhibiting melanin deposition and collagen degradation by downregulating MMP expression. Concentrations of malondialdehyde, tyrosinase, interleukin-6, interleukin- 12, and tumor necrosis factor-alpha in photoaged skin decreased, while SOD content in photodamaged HaCaT cells significantly increased. Trifarotene (3.3 μmol L-1) inhibited phosphorylated JNK and c-Jun expression both independently and collaboratively with the JNK activator anisomycin, demonstrating that trifarotene mitigates UV-induced collagen degradation and apoptosis through inhibition of the JNK/c-Jun/MMPs signaling pathway., (© 2024 Xuan Fei et al., published by Sciendo.)

Dynamic imaging of genomic loci is key for understanding gene regulation, but methods for imaging genomes, in particular non-repetitive DNAs, are limited. We developed CRISPRdelight, a DNA-labeling system based on endonuclease-deficient CRISPR-Cas12a (dCas12a), with an engineered CRISPR array to track DNA location and motion. CRISPRdelight enables robust imaging of all examined 12 non-repetitive genomic loci in different cell lines. We revealed the confined movement of the CCAT1 locus (chr8q24) at the nuclear periphery for repressed expression and active motion in the interior nucleus for transcription. We uncovered the selective repositioning of HSP gene loci to nuclear speckles, including a remarkable relocation of HSPH1 (chr13q12) for elevated transcription during stresses. Combining CRISPR-dCas12a and RNA aptamers allowed multiplex imaging of four types of satellite DNA loci with a single array, revealing their spatial proximity to the nucleolus-associated domain. CRISPRdelight is a user-friendly and robust system for imaging and tracking genomic dynamics and regulation., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Neurons are the primary cells responsible for information processing in the central nervous system (CNS). However, they are vulnerable to damage and insult in a variety of neurological disorders. As the most abundant glial cells in the brain, astrocytes provide crucial support to neurons and participate in synapse formation, synaptic transmission, neurotransmitter recycling, regulation of metabolic processes, and the maintenance of the blood-brain barrier integrity. Though astrocytes play a significant role in the manifestation of injury and disease, they do not work in isolation. Cellular interactions between astrocytes and neurons are essential for maintaining the homeostasis of the CNS under both physiological and pathological conditions. In this review, we explore the diverse interactions between astrocytes and neurons under physiological conditions, including the exchange of neurotrophic factors, gliotransmitters, and energy substrates, and different CNS diseases such as Alzheimer's disease, Parkinson's disease, stroke, traumatic brain injury, and multiple sclerosis. This review sheds light on the contribution of astrocyte-neuron crosstalk to the progression of neurological diseases to provide potential therapeutic targets for the treatment of neurological diseases., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: Tacrolimus remains the mainstay of immunosuppression in kidney transplantation. Understanding the relationship between therapeutic tacrolimus levels and outcomes of acute rejection, patient/graft survival, and tolerability are important. The relationship between time to therapeutic tacrolimus levels and outcomes has not been well established, specifically with the use of extended release tacrolimus formulation (LCP-Tac). This study investigated time to therapeutic tacrolimus levels of 2 tacrolimus formulations, LCP-Tac and immediate release tacrolimus (IR-Tac), as a predictor of clinical outcomes. Methods: This was a single-center, retrospective, cohort study of kidney transplant recipients at Duke Hospital between 2013-2021. The primary objective evaluated the difference in time to therapeutic tacrolimus levels with LCP-Tac vs IR-Tac regimens. Secondary endpoints included time within therapeutic range during the first 3 months post-transplant, incidence of biopsy-proven rejection, development of de novo donor specific antibodies, and patient and allograft survival at 12 months post-transplant. Results: 128 patients were included (63 in LCP-Tac group and 65 in IR-Tac group). The time to therapeutic tacrolimus level was similar between formulations (7.2 days with LCP-Tac compared to 6.7 days with IR-Tac, P = .63). The time within therapeutic range during the first 3 months post-transplant, via modified Rosendaal, was similar with LCP-Tac and IR-Tac (56.1% vs 64.8%, respectively). Rates of biopsy-proven acute rejection at 12 months were similar (7/63 (11.1%) compared to 4/65 (6.2%)). There was no difference in patient/graft survival between groups. Conclusions: The time to therapeutic tacrolimus levels did not differ based on tacrolimus formulation and was not correlated with clinical outcomes., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Natural gas, primarily composed of methane (CH 4 ), represent an excellent choice for a potentially sustainable renewable energy transition. However, the process of compressing and liquefying CH 4 for transport and storage typically results in significant energy losses. In addition, in order to optimize its efficacy as a fuel, the CH 4 content of natural gas needs to be increased to a level of at least 97 % to ensure its quality and efficiency in various applications. Metal-organic frameworks (MOFs) represent a novel category of porous materials that possess exceptional capability in modifying pore size and chemical environment, making them ideally suited for the storage of CH 4 and the adsorption of propane (C 3 H 8 ), ethane (C 2 H 6 ), carbon dioxide (CO 2 ), nitrogen (N 2 ), and hydrogen sulfide (H 2 S) to facilitate the purification process of CH 4 from natural gas. In this paper, we systematically summarize the mechanism by which MOF materials facilitate the storage of CH 4 and the purification of CH 4 from natural gas, leveraging the structural characteristics inherent to MOF materials. The focus of further research should also be directed towards the investigation of CH 4 storage by flexible MOFs, the resolution of the trade-off dilemma, and the commercial application of MOFs., (© 2024 Wiley-VCH GmbH.)

Humans use both model-free (or habitual) and model-based (or goal-directed) strategies in sequential decision-making. Working memory (WM) is essential for the model-based strategy; however, its exact role in these processes remains elusive. This study investigates the influence of WM processes on decision-making and the underlying cognitive computing mechanisms. Specifically, we used experimental data from two-stage decision tasks and found that delay and load, two WM-specific variables, impact goal-revisiting behaviors. Then, we proposed possible computational mechanisms by which WM participates in information processing and integrated them into the model-based system. The proposed Hybrid-WM model reproduced the observed experimental effects and fit human behavior better than the classic hybrid reinforcement learning model. These results were verified with independent data sets. Furthermore, differences in model parameters explain the age-related difference in sequential decision-making. Overall, this study suggests that WM guides action valuation in model-based strategies, highlighting the contribution of higher cognitive functions to sequential decision-making., (© 2024 Massachusetts Institute of Technology.)

There is a profound need to identify modifiable risk factors to screen and prevent pancreatic cancer. Air pollution, including fine particulate matter (PM2.5), is increasingly recognized as a risk factor for cancer. We conducted a case-control study using data from the electronic health record (EHR) of Duke University Health System, 15-year residential history, NASA satellite fine particulate matter (PM2.5) and neighborhood socioeconomic data. Using deterministic and probabilistic linkage algorithms, we linked residential history and EHR data to quantify long term PM2.5 exposure. Logistic regression models quantified the association between a one interquartile range (IQR) increase in PM2.5 concentration and pancreatic cancer risk. The study included 203 cases and 5027 controls (median age of 59 years, 62% female, 26% Black). Individuals with pancreatic cancer had higher average annual exposure (9.4 μg/m3) as compared to IQR increase in average annual PM2.5 was associated with greater odds of pancreatic cancer (OR=1.20; 95% CI: 1.00-1.44). These findings highlight the link between elevated PM2.5 exposure and increased pancreatic cancer risk. They may inform screening strategies for high-risk populations and guide air pollution policies to mitigate exposure., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The attention network test (ANT), developed based on the triple-network taxonomy by Posner and colleagues, has been widely used to examine the efficacy of alerting, orienting and executive control in clinical and developmental neuroscience studies. Recent research suggests the imperfect reliability of the behavioural ANT and its variants. However, the classical ANT fMRI task's test-retest reliability has received little attention. Moreover, it remains ambiguous whether the attention-related intrinsic network components, especially the dorsal attention, ventral attention and frontoparietal network, manifest acceptable reliability. The present study approaches these issues by utilizing an openly available ANT fMRI dataset for participants with Parkinson's disease and healthy elderly. The reproducibility of group-level activations across sessions and participant groups and the test-retest reliability at the individual level were examined at the voxel, region and network levels. The intrinsic network was defined using the Yeo-Schaefer atlas. Our results reveal three critical facets: (1) the overlapping of the group-level contrast map between sessions and between participant groups was unsatisfactory; (2) the reliability of alerting, orienting and executive, defined as a contrast between conditions, was worse than estimates of specific conditions. (3) Dorsal attention, ventral attention, visual and somatomotor networks showed acceptable reliability for the congruent and incongruent conditions. Our results suggest that specific condition estimates might be used instead of the contrast map for individual or group-difference studies., (© 2024 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Z-discs are core ultrastructural organizers of cardiomyocytes that modulate many facets of cardiac pathogenesis. Yet a comprehensive proteomic atlas of Z-disc-associated components remain incomplete. Here, we established an adeno-associated virus (AAV)-delivered, cardiomyocyte-specific, proximity-labeling approach to characterize the Z-disc proteome in vivo. We found palmdelphin (PALMD) as a novel Z-disc-associated protein in both adult murine cardiomyocytes and human pluripotent stem cell-derived cardiomyocytes. Germline and cardiomyocyte-specific Palmd knockout mice were grossly normal at baseline but exhibited compromised cardiac hypertrophy and aggravated cardiac injury upon long-term isoproterenol treatment. By contrast, cardiomyocyte-specific PALMD overexpression was sufficient to mitigate isoproterenol-induced cardiac injury. PALMD ablation perturbed the transverse tubule (T-tubule)-sarcoplasmic reticulum (SR) ultrastructures, which formed the Z-disc-associated junctional membrane complex (JMC) essential for calcium handling and cardiac function. These phenotypes were associated with the reduction of nexilin (NEXN), a crucial Z-disc-associated protein that is essential for both Z-disc and JMC structures and functions. PALMD interacted with NEXN and enhanced its protein stability while the Nexn mRNA level was not affected. AAV-based NEXN addback rescued the exacerbated cardiac injury in isoproterenol-treated PALMD-depleted mice. Together, this study discovered PALMD as a potential target for myocardial protection and highlighted in vivo proximity proteomics as a powerful approach to nominate novel players regulating cardiac pathogenesis., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Patients with hemorrhagic stroke have high rates of morbidity and mortality, and drugs for prevention are very limited. Mendelian randomization (MR) analysis can increase the success rate of drug development by providing genetic evidence. Previous MR analyses only analyzed the role of individual drug target genes in hemorrhagic stroke; therefore, we used MR analysis to systematically explore the druggable genes for hemorrhagic stroke. We sequentially performed summary-data-based MR analysis and two-sample MR analysis to assess the associations of all genes within the database with intracranial aneurysm, intracerebral hemorrhage, and their subtypes. Validated genes were further analyzed by colocalization. Only genes that were positive in all three analyses and were druggable were considered desirable genes. We also explored the mediators of genes affecting hemorrhagic stroke incidence. Finally, the associations of druggable genes with other cardiovascular diseases were analyzed to assess potential side effects. We identified 56 genes that significantly affected hemorrhagic stroke incidence. Moreover, TNFSF12, SLC22A4, SPARC, KL, RELT, and ADORA3 were found to be druggable. The inhibition of TNFSF12, SLC22A4, and SPARC can reduce the risk of intracranial aneurysm, subarachnoid hemorrhage, and intracerebral hemorrhage. Gene-induced hypertension may be a potential mechanism by which these genes cause hemorrhagic stroke. We also found that blocking these genes may cause side effects, such as ischemic stroke and its subtypes. Our study revealed that six druggable genes were associated with hemorrhagic stroke, and the inhibition of TNFSF12, SLC22A4, and SPARC had preventive effects against hemorrhagic strokes., (© 2024. The Author(s).)

Nitrogen loss from rice systems is an important source of agricultural non-point source pollution. Many studies revolve around reducing the rate of nitrogen fertilizer application. However, studies examining the characteristics of nitrogen loss in multiple loss paths （runoff, leaching, and lateral seepage） under different straw and fertilizer managements are lacking. Therefore, a study was carried out based on a rice field planted for more than 20 years with straw continuously returned to the field for more than 5 years in Taihu lake basin. The effects of straw and fertilizer managements on nitrogen loss in different paths during the whole growth period of rice were studied. Moreover, straw and fertilizer managements were evaluated by their production suitability and environmental friendliness based on crop yield, nitrogen use efficiency, and nitrogen loss. The results showed that straw removal from the field increased the response sensitivity of nitrogen accumulation in plant tissue to nitrogen application. The nitrogen loss in the rice season was 9-17 kg·hm -2 , accounting for 5%-7% of the nitrogen application rate. Straw removal increased the risk of nitrogen loss when soaking water discharged. Straw returning could decrease the nitrogen loss by more than 15%, though the effect of straw on nitrogen loss via lateral seepage was not clear. Furthermore, the suitable substitution of organic fertilizer （30% in this study） could respectively reduce the amount of nitrogen loss via runoff, leaching, and lateral seepage by 16%, 26%, and 37% compared with the fertilizer application under the same nitrogen gradient. In conclusion, the implementation of straw returning and fertilizer type optimization measures effectively reduced the nitrogen loss for unit weight of rice production and realized the balance between agricultural production and environmental protection.

Background: Epilepsy affects 1% to 2% of the global population, and those who are resistant to medical treatment may be candidates for neuromodulation. In select populations, brain stimulation approaches including deep brain stimulation (DBS) and responsive neurostimulation (RNS) are used. Although studies have shown that patients from Black, Hispanic, lower income, and rural communities have less access to epilepsy care and have lower rates of epilepsy surgery, disparities in the use of brain stimulation for epilepsy treatment are currently not known., Materials and Methods: We queried the US National Inpatient Sample data base from January 1, 2014 to December 31, 2019 for all patients discharged with an International Classification of Diseases (ICD) Ninth Revision or ICD Tenth Revision diagnosis of drug-resistant epilepsy. Among these patients discharged, the rates of brain stimulation treatment, including DBS and RNS, were reported in each subgroup of race, ethnicity, and insurance. To generate national estimates, all analyses were weighted., Results: A total of 237,895 patients discharged with drug-resistant epilepsy were identified, of whom 4,925 (2.1%) received brain stimulation treatment for drug-resistant epilepsy. Black patients (n = 420, 0.9%, odds ratio [OR] = 0.51, 95% CI [0.40, 0.64]) were less likely to receive brain stimulation treatment than were White patients (n = 3300, 2.4%). There was no significant difference between Asian (n = 105, 2.3%, OR = 0.80, 95% CI [0.53, 1.33]) and Hispanic (n = 655, 2.6%, OR = 0.95, 95% CI [0.77, 1.17]) patients and White patients. No significant difference was observed between female (n = 2515, 2.1%, OR = 1.02, 95% CI [0.89, 1.17]) and male (n = 2410, 2.0%) patients either. Patients with Medicare (n = 1150, 1.2%, OR = 0.69, 95% CI [0.57, 0.84]) or Medicaid (n = 1150, 1.8%, OR = 0.52, 95% CI [0.44, 0.62]) were less likely to receive brain stimulation treatment than were those with private insurance as the primary payer (n = 2370, 3.9%)., Conclusions: We discovered significant disparities in the use of brain stimulation treatments for drug-resistant epilepsy based on race and insurance status. More research will be required to determine the cause of these disparities., Competing Interests: Conflict of Interest Shervin Rahimpour reports consulting fees from Boston Scientific and speaker fees from Abbott. The remaining authors reported no conflict of interest., (Copyright © 2023 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

The human brain is localized and distributed. On the one hand, each cognitive function tends to involve one hemisphere more than the other, also known as the principle of lateralization. On the other hand, interactions among brain regions in the form of functional connectivity (FC) are indispensable for intact function. Recent years have seen growing interest in the association between lateralization and FC. However, FC metrics vary from spurious correlation to causal associations. If lateralization manifests local processing and causal network interactions, more causally valid FC metrics should predict lateralization index (LI) better than FC based on simple correlations. The present study directly investigates this hypothesis within the activity flow framework to compare the association between lateralization and four brain connectivity metrics: correlation-based FC, multiple-regression FC, partial-correlation FC, and combinedFC. We propose two modeling approaches: the one-step approach, which models the relationship between LI and FC directly, and the two-step approach, which predicts the brain activation and calculates the LI. Our results indicated that multiple-regression FC, partial-correlation FC, and combinedFC could significantly improve the model prediction compared to correlation-based FC, which was consistent in a spatial working memory task (typically right-lateralized) and a language task (typically left-lateralized). The one-step and two-step approach yielded similar conclusions. In addition, the finding was replicated in a clinical sample of schizophrenia (SZ), bipolar disorder (BP), and attention deficit hyperactivity disorder (ADHD). The present study suggests that the causal interactions among brain regions help shape the lateralization pattern., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Essential tremor (ET) is a movement disorder that affects 4%-5% of adults >65 years. For patients with medically refractory ET, neurosurgical interventions such as deep brain stimulation (DBS) and unilateral MR-guided focused ultrasound thalamotomy (MRgFUS) are available. In this retrospective cohort study, we examined the demographics of patients with ET who have received MRgFUS and evaluated trends in DBS usage in the USA after the introduction of MRgFUS in 2016., Methods: We used multiple databases to examine the demographics of patients who received DBS and MRgFUS, and trends in DBS. To assess the demographics, we queried the TriNetX database from 2003 to 2022 to identify patients diagnosed with ET and stratify them by DBS or MRgFUS treatment by using Current Procedural Terminology codes. Patient demographics were reported as frequencies and percentages. To examine the trends in DBS for ET, the yearly frequency of DBS procedures done for ET between 2012 and 2019 was extracted from the National Inpatient Sample (NIS) database, and breakpoint analysis was performed. Additionally, the yearly frequency of MRgFUS procedures for ET was obtained from Insightec Exlabate., Results: Most of the patients (88.69%) in the cohort extracted from TriNetX database self-identified as white, followed by black or African American (2.40%) and Asian (0.52%). A higher percentage of black patients received MRgFUS treatment than DBS (4.10% vs 1.88%). According to the NIS database, from 2012 to 2020, 13 525 patients received DBS for ET., Conclusion: This study provides an overview of the characteristics of patients who undergo DBS or MRgFUS. We found notable differences in sex and race among patients who underwent each treatment type. Additionally, until at least the beginning of 2020, the number of DBS procedures for ET was not negatively affected after the introduction of MRgFUS., Competing Interests: Competing interests: SR receives consulting, and/or speaker fees from Abbott and Boston Scientific., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Significance: Optical imaging is a non-invasive imaging technology that utilizes near-infrared light, allows for the image reconstruction of optical properties like diffuse and absorption coefficients within the tissue. A recent trend is to use signal processing techniques or new light sources and expanding its application., Aim: We aim to develop the reflective optical imaging using the chaotic correlation technology with chaotic laser and optimize the quality and spatial resolution of reflective optical imaging., Approach: Scattering medium was measured using reflective configuration in different inhomogeneous regions to evaluate the performance of the imaging system. The accuracy of the recovered optical properties was investigated. The reconstruction errors of absorption coefficients and geometric centers were analyzed, and the feature metrics of the reconstructed images were evaluated., Results: We showed how chaotic correlation technology can be utilized for information extraction and image reconstruction. This means that a higher signal-to-noise ratio and image reconstruction of inhomogeneous phantoms under different scenarios successfully were achieved., Conclusions: This work highlights that the peak values of correlation of chaotic exhibit smaller reconstruction error and better reconstruction performance in optical imaging compared with reflective optical imaging with the continuous wave laser., (© 2024 The Authors.)

Background: Chronic low back pain is a leading cause of morbidity and is among the largest cost drivers for the healthcare system. Research on healthcare resource utilization of patients with low back pain who are not surgical candidates is limited, and few studies follow individuals who generate high healthcare costs over time., Purpose: This claims study aimed to identify patients with high-impact mechanical, chronic low back pain (CLBP), quantify their low back pain-related health resource utilization, and explore associated patient characteristics. We hypothesize that patients in the top quartile of healthcare resource utilization in the second year after initial diagnosis will continue to generate considerable back pain-related costs in subsequent years., Study Design/setting: IBM MarketScan Research Databases from 2009-2019 were retrospectively analyzed., Patient Sample: Adults in the United States with an initial diagnosis of low back pain between 2010 and 2014 who did not have cancer, spine surgery, recent pregnancy, or inflammatory spine conditions, were identified using the International Classification of Diseases (ICD) and Current Procedural Terminology (CPT) codes. To ensure patients had chronic low back pain, it was required that individuals had additional claims with a low back pain diagnosis 6 to 12 and 12 to 24 months after initial diagnosis., Outcome Measures: Cost and utilization of inpatient visits, outpatient visits, emergency room visits, pharmacologic and nonpharmacologic treatment options and imaging for chronic low back pain., Methods: Annual back pain-related costs and the use of pharmacologic and nonpharmacologic treatments for 5 years were analyzed. Logistic regression was utilized to identify factors associated with persistent high spending., Results: Of 16,917 individuals who met the criteria for chronic low back pain, 4,229 met the criteria for having high healthcare utilization, defined as being in the top quartile of back pain-related costs in the 12 to 24 months after their initial diagnosis. The mean and median back pain-related cost in the first year after an initial diagnosis was $7,112 (SD $9,670) and $4,405 (Q1 $2,147, Q3 $8,461). Mean and median back pain related costs in the second year were $11,989 (SD $20,316) and $5,935 (Q1 $3,892, Q3 $10,678). Costs continued to be incurred in years 3 to 5 at a reduced rate. The cumulative mean cost for back pain over the 5 years following the initial diagnosis was $31,459 (SD $39,545). The majority of costs were from outpatient services. Almost a quarter of the high utilizers remained in the top quartile of back pain-related costs during years 3 to 5 after the initial diagnosis, and another 19% remained in the top quartile for 2 of the 3 subsequent years. For these two groups combined (42%), the 5-year cumulative mean cost for back pain was $43,818 (SD $48,270). Patient characteristics associated with a higher likelihood of remaining as high utilizers were diabetes, having a greater number of outpatient visits and pharmacologic prescriptions, and lower utilization of imaging services., Conclusion: This is one of the first studies to use an administrative claims database to identify high healthcare resource utilizers among a population of United States individuals with nonsurgical, chronic low back pain and follow their utilization over time. There was a population of individuals who continued to experience high costs 5 years beyond their initial diagnosis, and the majority of individuals continued to seek outpatient services. Further longitudinal claims research that incorporates symptom severity is needed to understand the economic implications of this condition., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Ferroptosis is an iron-dependent form of programmed cell death (PCD) and ischemic stroke (IS) has been confirmed to be closely related to ferroptosis. The mechanisms of ferroptosis were summarized into three interrelated aspects: iron metabolism, lipid peroxide metabolism, as well as glutathione and amino acid metabolism. What's more, the causal relationship between ferroptosis and IS has been elucidated by several processes. The disruption of the blood-brain barrier, the release of excitatory amino acids, and the inflammatory response after ischemic stroke all lead to the disorder of iron metabolism and the antioxidant system. Based on these statements, we reviewed the reported effects of compounds and drugs treating IS by modulating key molecules in ferroptosis. Through detailed analysis of the roles of these key molecules, we have also more clearly demonstrated the essential effect of ferroptosis in the occurrence of IS so as to provide new targets and ideas for the therapeutic targets of IS., (© 2024. The Author(s).)

The heavy fermion physics is dictated by subtle competing exchange interactions, posing a challenge to their understanding. One-dimensional (1D) Kondo lattice model has attracted special attention in theory, because of its exact solvability and expected unusual quantum criticality. However, such experimental material systems are extremely rare. Here, we demonstrate the realization of quasi-1D Kondo lattice behavior in a monolayer van der Waals crystal NbSe 2 , that is driven into a stripe phase via Se-deficient line defects. Spectroscopic imaging scanning tunneling microscopy measurements and first-principles calculations indicate that the stripe-phase NbSe 2 undergoes a novel charge-density wave transition, creating a matrix of local magnetic moments. The Kondo lattice behavior is manifested as a Fano resonance at the Fermi energy that prevails the entire film with a high Kondo temperature. Importantly, coherent Kondo screening occurs only in the direction of the stripes. Upon approaching defects, the Fano resonance exhibits prominent spatial 1D oscillations along the stripe direction, reminiscent of Kondo holes in a quasi-1D Kondo lattice. Our findings provide a platform for exploring anisotropic Kondo lattice behavior in the monolayer limit., (© 2024. The Author(s).)

Objective: Deep brain stimulation (DBS) is a well-established treatment for Parkinson's disease (PD) and essential tremor (ET). Although the prevalence of PD and ET can vary by sex and race, little is known about the accessibility of neurosurgical treatments for these conditions. In this nationwide study, the authors aimed to characterize trends in the use of DBS for the treatment of PD and ET and to identify disparities in the neurosurgical treatment of these diseases based on ethnic, racial, sex, insurance, income, hospital, and geographic factors., Methods: Using the dates January 1, 2012, to December 31, 2019, the authors queried the National Inpatient Sample database for all discharges with an ICD-9 or ICD-10 diagnosis of PD or ET. Among these discharges, the DBS rates were reported for each subgroup of race, ethnicity, and sex. To develop national estimates, all analyses were weighted., Results: Among 2,517,639 discharges with PD, 29,820 (1.2%) received DBS, and among 652,935 discharges with ET, 11,885 (1.8%) received DBS. Amid the PD cases, Black patients (n = 405 [0.2%], OR 0.16, 95% CI 0.12-0.20) were less likely than White patients (n = 23,975 [1.2%]) to receive DBS treatment, as were Hispanic patients (n = 1965 [1.1%], OR 0.76, 95% CI 0.65-0.88), whereas Asian/Pacific Islander patients (n = 855 [1.5%]) did not statistically differ from White patients. Amid the ET cases, Black (n = 230 [0.8%], OR 0.39, 95% CI 0.27-0.56), Hispanic (n = 215 [1.0%], OR 0.39, 95% CI 0.28-0.55), and Asian/Pacific Islander (n = 55 [1.0%], OR 0.51, 95% CI 0.28-0.93) patients were less likely than White patients (n = 10,440 [1.9%]) to receive DBS. Females were less likely than males to receive DBS for PD (OR 0.69, p < 0.0001) or ET (OR 0.70, p < 0.0001)., Conclusions: The authors describe significant racial and sex-based differences in the utilization of DBS for the treatment of PD and ET. Further research is required to ascertain the causes of these disparities, as well as any differences in access to specialty neurosurgical care and referral for neuromodulation approaches.

Executive function is vital for normal social, cognitive, and motor functions. Executive function decline due to aging increases the risk of disability and falls in older adults, which has become an urgent public health issue. Fast and convenient neuropsychological tools are thus needed to identify high-risk groups as early as possible to conduct a timely intervention. Card sorting tasks, such as Wisconsin Card Sorting Task (WCST) and its variants, are popular tools for measuring executive function. This study investigated the reliability of an open-source, self-administered, online, short-version card sorting task with a sample of young (n = 107, 65 females, age: M = 30.1 years, SD = 5.5 years) and elderly Chinese (n = 113, 53 females, age: M = 64.0 years, SD = 6.7 years). We developed an automated scoring and visualization procedure following the recent recommendations on scoring perseverative responses to make the results comparable to the standardized WCST. Reliability estimates of commonly used measures were calculated using the split-half method. All task indices' reliabilities were reasonably good in both old and young groups except for "failure-to-maintain-set." Elderly Chinese adults showed compromised task performance on all measures compared with the young Chinese adults at the group level. The R script of automated scoring and estimation of reliability is publicly available., (© 2023. The Psychonomic Society, Inc.)

Objective: While current research suggests potential value for docosahexaenoic acid (DHA) in the prevention and management of atopic dermatitis (AD), the causal relationship between DHA and AD remains unclear, and the underlying mechanisms are not well understood., Materials and Methods: To investigate the potential causal relationship between DHA and AD, as well as to explore potential mediating mechanisms, we employed the Mendelian randomization (MR) methods. To study these potential relationships, we conducted MR analysis using publicly available Genome-Wide Association Studies (GWAS) data. Effect estimates were computed using the random-effects inverse-variance weighted method., Results: Our study demonstrates a negative correlation between DHA levels and AD risk (OR: 0.915, 95% CI: 0.858-0.975, p=0.007). Furthermore, in MR analysis using tumor necrosis factor ligand superfamily member 14 (TNFSF14) levels as an outcome, DHA levels also show a negative association with TNFSF14 levels (OR: 0.933, 95% CI: 0.879-0.990, p=0.022). Subsequently, we performed further analysis to explore the relationship between TNFSF14 and AD risk, revealing a positive correlation (OR: 1.069, 95% CI: 1.005-1.137, p=0.033). This suggests a potential mediating role of TNFSF14 in the impact of DHA on AD risk., Conclusions: In summary, our study employs MR analysis to offer genetic evidence indicating a potential role of DHA in reducing the risk of AD, as well as opening avenues for further in-depth investigation into potential mechanisms. These findings emphasize the importance of ongoing research in this field.

Background: There has been heightened interest in performing percutaneous lumbar interbody fusions (percLIFs) through Kambin's triangle, an anatomic corridor allowing entrance into the disc space. However, due to its novelty, there are limited data regarding the long-term benefits of this procedure. Our objective was to determine the long-term efficacy and durability of the percutaneous insertion of an expandable titanium cage through Kambin's triangle without facetectomy., Methods: A retrospective review of patients undergoing percLIF via Kambin's triangle using an expandable titanium cage was performed. Demographics, visual analog scale (VAS) scores, Oswestry Disability Index (ODI), radiographic measurements, perioperative variables, and complications were recorded. VAS, ODI, and radiographic measurements were compared with baseline using the generalized estimating equations assuming normally distributed data. Fusion was assessed with computed tomography (CT) at 1 and 2 years after the procedure., Results: A total of 49 patients were included. Spondylolisthesis, lumbar lordosis (LL), sacral slope, pelvic tilt, and anterior/posterior disc space height were all significantly improved postoperatively at each time point of 3, 6, 12, and 24 months ( P < 0.001). Pelvic incidence-LL mismatch decreased significantly at each follow-up ( P < 0.001) with a mean reduction of 4° by 24 months. VAS back scores reduced by >2 points at the 6, 12, and 24 month follow-ups. ODI scores reduced by >15 points at the 12- and 24-month follow-ups. Of the patients who had 1- and 2-year CT images, fusion rates at those time points were 94.4% (17/18) and 87.5% (7/8), respectively. The mean annual rate of surgically significant adjacent segment disease was 2.74% through an average follow-up of 2.74 years., Conclusion: These results highlight that percLIF, a procedure done without an endoscope or facetectomy, can be performed using an expandable titanium cage through Kambin's triangle with excellent radiographic and clinical results., Clinical Relevance: percLIF via Kambin's triangle is a safe and succesful procedure with long-term improvements in both clinical and radiographic outcomes., Competing Interests: Declaration of Conflicting Interests : Dr Abd-El-Barr is a consultant for Spineology, TrackX, and Depuy. Dr Shaffrey has financial relationships with NuVasive, Medtronic, SI Bone, and Proprio. Dr Wiggins is a strategic advisor for Qure.ai. Dr Chi discloses consulting fees from DePuy and K2M. The authors report that there are no other relevant disclosures pertaining to the content of this manuscript., (This manuscript is generously published free of charge by ISASS, the International Society for the Advancement of Spine Surgery. Copyright © 2023 ISASS. To see more or order reprints or permissions, see http://ijssurgery.com.)

Neuropsychiatric disorder (ND) is often accompanied by abnormal functional connectivity (FC) patterns in specific task contexts. The distinctive task-specific FC patterns can provide valuable features for ND classification models using deep learning. However, most previous studies rely solely on the whole-brain FC matrix without considering the prior knowledge of task-specific FC patterns. Insight by the decoding studies on brain-behavior relationship, we develop TSP-GNN, which extracts task-specific prior (TSP) connectome patterns and employs graph neural network (GNN) for disease classification. TSP-GNN was validated using publicly available datasets. Our results demonstrate that different ND types show distinct task-specific connectivity patterns. Compared with the whole-brain node characteristics, utilizing task-specific nodes enhances the accuracy of ND classification. TSP-GNN comprises the first attempt to incorporate prior task-specific connectome patterns and the power of deep learning. This study elucidates the association between brain dysfunction and specific cognitive processes, offering valuable insights into the cognitive mechanism of neuropsychiatric disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lang, Yang and Li.)

Microglia are activated following cerebral ischemic insult. P-glycoprotein (P-gp) is an efflux transporter on microvascular endothelial cells and upregulated after cerebral ischemia. This study evaluated the effects and possible mechanisms of P-gp on microglial polarization/activation in mice after ischemic stroke. P-gp-specific siRNA and adeno-associated virus (p-AAV) were used to silence and overexpress P-gp, respectively. Middle cerebral artery occlusion/reperfusion (MCAO/R) and oxygen-glucose deprivation/reoxygenation (OGD/R) were performed in mice and cerebral microvascular endothelial cells (bEnd.3) in vitro , respectively. OGD/R-injured bEnd.3 cells were cocultured with mouse microglial cells (BV2) in Transwell. Influences on acute ischemic stroke outcome, the expression of inflammatory cytokines, and chemokines and chemokines receptors, microglial polarization, glucocorticoid receptor (GR) nuclear translocation, and GR-mediated mRNA decay (GMD) activation were evaluated via reverse transcription real-time polymerase chain reaction, western blot, or immunofluorescence. Silencing P-gp markedly alleviated experimental ischemia injury as indicated by reduced cerebral infarct size, improved neurological deficits, and reduced the expression of interleukin-6 (IL-6) and IL-12 expression. Silencing P-gp also mitigated proinflammatory microglial polarization and the expression of C-C motif chemokine ligand 2 (CCL2) and its receptor CCR2 expression, whereas promoted anti-inflammatory microglia polarization. Additionally, P-gp silencing promoted GR nuclear translocation and the expression of GMD relative proteins in endothelial cells. Conversely, overexpressing P-gp via p-AAV transfection offset all these effects. Furthermore, silencing endothelial GR counteracted all effects mediated by silencing or overexpressing P-gp. Elevated P-gp expression aggravated inflammatory response and brain damage after ischemic stroke by augmenting proinflammatory microglial polarization in association with increased endothelial CCL2 release due to GMD inhibition by P-gp., Competing Interests: No author has an actual or perceived conflicts of interest with the contents of this article., (Copyright © 2023 Yan Chen et al.)

Objective: Preoperative assessment is important for neurosurgical risk stratification, but the level of evidence for individual screening tests is low. In preoperative urinalysis (UA), testing may significantly increase costs and lead to inappropriate antibiotic treatment. We prospectively evaluated whether eliminating preoperative UA was noninferior to routine preoperative UA as measured by 30-day readmission for surgical site infection in adult elective neurosurgical procedures., Methods: A single-institution prospective, pragmatic study of patients receiving elective neurosurgical procedures from 2018 to 2020 was conducted. Patients were allocated based on same-day versus preoperative admission status. Rates of preoperative UA and subsequent wound infection were measured along with detailed demographic, surgical, and laboratory data., Results: The study included 879 patients. The most common types of surgery were cranial (54.7%), spine (17.4%), and stereotactic/functional (19.5%). No preoperative UA was performed in 315 patients, while 564 underwent UA. Of tested patients, 103 (18.3%) met criteria for suspected urinary tract infection, and 69 (12.2%) received subsequent antibiotic treatment. There were 14 patients readmitted within 30 days (7 without UA [2.2%] vs. 7 with UA [1.2%]) for subsequent wound infection with a risk difference of 0.98% (95% confidence interval -0.89% to 2.85%). The upper limit of the confidence interval exceeded the preselected noninferiority margin of 1%., Conclusions: In this prospective study of preoperative UA for elective neurosurgical procedures using a pragmatic, real-world design, risk of readmission due to surgical site infection was very low across the study cohort, suggesting a limited role of preoperative UA for elective neurosurgical procedures., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: High-frequency spinal cord stimulation (HF-SCS) is a treatment option for postsurgical persistent spinal pain syndrome (type 2 PSPS). We aimed to determine the health care costs associated with this therapy in a nationwide cohort., Materials and Methods: IBM Marketscan® Research Databases were used to identify patients who underwent HF-SCS implantation from 2016 to 2019. Inclusion criteria included prior spine surgery or diagnoses of PSPS or postlaminectomy pain syndrome any time within the two years before implantation. Inpatient and outpatient service costs, medication costs, and out-of-pocket costs were collected six months before implantation (baseline) and one, three, and six months after implantation. The six-month explant rate was calculated. Costs were compared between baseline and six months after implant via Wilcoxon sign rank test., Results: In total, 332 patients were included. At baseline, patients incurred median total costs of $15,393 (Q1: $9,266, Q3: $26,216), whereas the postimplant median total costs excluding device acquisition were $727 (Q1: $309, Q3: $1,765) at one month, $2,840 (Q1: $1,170, Q3: $6,026) at three months, and $6,380 (Q1: $2,805, Q3: $12,637) at six months. The average total cost was reduced from $21,410 (SD $21,230) from baseline to $14,312 (SD $25,687) at six months after implant for an average reduction of $7,237 (95% CI = $3212-$10,777, p < 0.001). The median device acquisition costs were $42,937 (Q1: $30,102, Q3: $65,880). The explant rate within six months was 3.4% (8/234)., Conclusions: HF-SCS for PSPS was associated with significant decreases in total health care costs and offsets acquisition costs within 2.4 years. With the rising incidence of PSPS, it will be critical to use clinically effective and cost-efficient therapies for treatment., (Copyright © 2023 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

Background: Chronic spasticity causes significant impairment and financial burden. Oral baclofen, the first-line therapy, can have intolerable, dose-dependent side effects. Targeted drug delivery (TDD) through intrathecal baclofen delivers smaller amounts of baclofen into the thecal sac via an implanted infusion system. However, the health care resource utilization of patients with spasticity receiving TDD has not been studied extensively., Materials and Methods: Adult patients who received TDD for spasticity between 2009 and 2017 were identified using the IBM MarketScan® data bases. Patients' use of oral baclofen and health care costs were examined at baseline (one year before implantation) and three years after implantation. A multivariable regression model using the generalized estimating equations method and a log link function was used to compare postimplantation costs with those at baseline., Results: The study identified 771 patients with TDD for medication analysis and 576 for cost analysis. At baseline, the median costs were $39,326 (interquartile range [IQR]: $19,526-$80,679), which increased to $75,728 (IQR: $44,199-$122,676) in year 1, decreased to $27,160 (IQR: $11,896-$62,427) in year 2, and increased slightly to $28,008 (IQR: $11,771-$61,885) in year 3. In multivariable analysis, the cost was 47% higher than at baseline (cost ratio [CR] 1.47, 95% CI: 1.32-1.63) in year 1 but was 25% lower (CR 0.75, 95% CI: 0.66-0.86) in year 2 and 32% lower (CR 0.68, 95% CI: 0.59-0.79) in year 3. Before implant, 58% of patients took oral baclofen, which decreased to 24% by year 3. The median daily baclofen dose decreased from 61.8 mg (IQR: 40-86.4) before TDD to 32.8 mg (IQR: 30-65.7) three years later., Conclusions: Our findings indicate that patients who undergo TDD use less oral baclofen, potentially reducing the risk of side effects. Although total health care costs increased immediately after TDD, most likely owing to device and implantation costs, they decreased below baseline after one year. The costs of TDD reach cost neutrality approximately three years after implant, indicating its potential for long-term cost savings., (Copyright © 2023 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

The intensity of crop farming fertilizer input is generally high in the Taihu Lake Region, with chemical fertilizer as the main form. Due to inappropriate fertilizer application, nitrogen and phosphorus loss have occurred, causing serious agricultural non-point source pollution. The Ministry of Agriculture and Rural Affairs of China has launched the "zero-growth action for chemical fertilizer use" and "replacement action with organic fertilizer" ("two actions" for short) campaigns since 2015. Local agricultural sectors adjusted fertilizer application strategies of crop farming to respond to the call of two actions. However, the current research is still focusing on reducing the total amount of fertilizer application and increasing the area of organic fertilizer application, which is mainly based on grain crops. The study of agricultural environment problems is still lacking, especially in vegetable, orchard, and tea systems. Therefore, a study was carried out in the typical agricultural area of Suzhou City Wuzhong District from 2019 to 2021. Based on the data of the amount of nitrogen and phosphorus removal by harvest crops and soil nitrogen and phosphorus residual in paddy, vegetable, orchard, and tea systems, the loss was estimated. The responses of nitrogen and phosphorus loss from typical crop systems to fertilizer application strategy adjustments were studied through analysis of different factors. The results showed that fertilizer application rate was the key to control nitrogen and phosphorus loss. Additionally, the suitable replacement ratio of organic fertilizer could further reduce the loss risk. It should be noted that the urgent demand for nutrients in crop growth should be considered to determine the timing of organic fertilizer application, and agricultural machinery should be used to assist organic fertilizer application to reduce labor output if possible. Fertilizer efficiency was the core of environmental friendliness and economic benefits of crop farming. Hence, improving fertilizer efficiency should be the guidance of fertilizer application strategy adjustment. Our suggestions on the adjustment of fertilizer application strategy in different crop systems in the study area are as follows:attention should be paid to the nitrogen, phosphorus, and potassium input ratio in paddy systems to further reduce nitrogen and phosphorus loss. Planting structure adjustment should be emphasized in vegetable systems to promote fertilizer efficiency. The strategy to satisfy both tea and orchard growth from a composite system perspective would help to build crop systems that meet the needs of green agricultural development.

Background/objective: Education is at the core of neurosurgical residency, but little research in to the cost of neurosurgical education exists. This study aimed to quantify costs of resident education in an academic neurosurgery program using traditional teaching methods and the Surgical Autonomy Program (SAP), a structured training program., Methods: SAP assesses autonomy by categorizing cases into zones of proximal development (opening, exposure, key section, and closing). All first-time, 1-level to 4-level anterior cervical discectomy and fusion (ACDF) cases between March 2014 and March 2022 from 1 attending surgeon were divided into 3 groups: independent cases, cases with traditional resident teaching, and cases with SAP teaching. Surgical times for all cases were collected and compared within levels of surgery between groups., Results: The study found 2140 ACDF cases, with 1758 independent, 223 with traditional teaching, and 159 with SAP. For 1-level to 4-level ACDFs, teaching took longer than it did with independent cases, with SAP teaching adding additional time. A 1-level ACDF performed with a resident (100.1 ± 24.3 minutes) took about as long as a 3-level ACDF performed independently (97.1 ± 8.9 minutes). The average time for 2-level cases was 72.0 ± 18.2 minutes independently, 121.7 ± 33.7 minutes traditional, and 143.4 ± 34.9 minutes SAP, with significant differences among all groups., Conclusions: Teaching takes significant time compared with operating independently. There is also a financial cost to educating residents, because operating room time is expensive. Because attending neurosurgeons lose time to perform more surgeries when teaching residents, there is a need to acknowledge surgeons who devote time to training the next generation of neurosurgeons., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: This study aimed to determine whether SII on different days of admission is associated with severity and 180-day functional outcomes after basal ganglia ICH., Methods: In this retrospective study, data on baseline CT imaging characteristics, mRS, hematoma volume, and laboratory variables were included. The SII and NLR, LMR, and PLR were calculated from laboratory data collected on admission day, day 1, and days 5-7. Both univariate and multivariable logistic regression analyses were used to assess the association between the SII and the outcome. The receiver operating characteristic (ROC) analysis and area under the curve (AUC) were also used to evaluate the ability of the SII to predict outcomes., Result: A total of 245 patients were enrolled in the study. On different days, the NLR, PLR, and SII were significantly lower in patients with favorable outcomes than in those with poor outcomes, and the volume of hemorrhage was positively correlated with the SII. These parameters were associated with outcomes in the univariate logistic regression. In the adjusted analyses, the SII and PLR were independent predictors of basal ganglia ICH outcomes. ROC analysis revealed that the SII showed a stronger ability to predict the 6-month outcomes of patients after basal ganglia ICH than the PLR on different days (AUC = 0.642, 0.804, 0.827 vs. 0.592, 0.725, 0.757; all P  < 0.001)., Conclusion: The SII independently and strongly predicts the outcome of basal ganglia ICH. A high SII was associated with poor 6-month outcomes in patients with basal ganglia ICH., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (© 2023 The Authors.)

Objective: Despite advances in the nonsurgical management of cerebrovascular atherosclerotic steno-occlusive disease, approximately 15-20% of patients remain at high risk for recurrent ischemia. The benefit of revascularization with flow augmentation bypass has been demonstrated in studies of Moyamoya vasculopathy. Unfortunately, there are mixed results for the use of flow augmentation in atherosclerotic cerebrovascular disease. We conducted a study to examine the efficacy and long term outcomes of superficial temporal artery to middle cerebral artery (STA-MCA) bypass in patients with recurrent ischemia despite optimal medical management., Methods: A single-institution retrospective review of patients receiving flow augmentation bypass from 2013-2021 was conducted. Patients with non-Moyamoya vaso-occlusive disease (VOD) who had continued ischemic symptoms or strokes despite best medical management were included. The primary outcome was time to post-operative stroke. Time from cerebrovascular accident to surgery, complications, imaging results, and modified Rankin Scale (mRS) scores were aggregated., Results: Twenty patients met inclusion criteria. The median time from cerebrovascular accident to surgery was 87 (28-105.0) days. Only one patient (5%) had a stroke at 66 days post-op. One (5%) patient had a post-operative scalp infection, while 3 (15%) developed post-operative seizures. All 20 (100%) bypasses remained patent at follow-up. The median mRS score at follow up was significantly improved from presentation from 2.5 (1-3) to 1 (0-2), P = .013., Conclusions: For patients with high-risk non-Moyamoya VOD who have failed optimal medical therapy, contemporary approaches to flow augmentation with STA-MCA bypass may prevent future ischemic events with a low complication rate., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Abdelgadir et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Farmland is the important soil carbon pool of terrestrial ecosystems and organic nutrient pool for crop growth. To clarify the impact of climate warming on the soil carbon pool, this study analyzed the effects of warming and fertilization on soil organic carbon and its labile components under rice-wheat rotation using a free-air temperature increase system. The variation in soil carbon pool management index (CPMI) was also evaluated. The results showed that the combined effects of warming and fertilization on soil organic carbon content and labile organic carbon components were insignificant. Warming increased the soil organic carbon (SOC) content, and the differences between warming and the ambient control in total organic carbon (TOC) and recalcitrant organic carbon (ROC) reached a statistically significant level. Compared with those under the ambient control, the contents of TOC, ROC, and labile organic carbon (LOC) subjected to warming increased by 7.72%, 7.42%, and 10.11%, respectively. The increased microbial biomass carbon (MBC) content (20.4%) and decreased particulate organic carbon (POC) content (36.51%) may have been the main reason for the variation in SOC. Warming showed no significant effect on soil dissolved organic carbon (DOC) content, whereas it markedly reduced its soluble microbial by-product components (41.89%). The results also showed that fertilization had no significant effect on soil TOC, ROC, and LOC, but it notably reduced the contents of DOC and POC and increased the MBC content. Compared with those under the control without fertilization, the contents of DOC and POC subjected to fertilization decreased by 35.44% and 28.33%, respectively, and the MBC content increased by 33.38%. Additionally, fertilization tended to increase the anthropogenic humus component (5.13%) and soluble microbial by-product component (29.41%) in dissolved organic matter and reduce the terrestrial humus component (13.33%). Warming and fertilization both tended to improve soil CPMI. Affected by SOC and LOC, the increase in soil carbon pool index and soil lability index were the main reason for the increase in soil CPMI under warming and fertilization, respectively. Overall, the results revealed that climate warming can affect the soil carbon pool by changing soil labile carbon components, which are not affected by fertilization.

The nucleolus is the most prominent membraneless condensate in the nucleus. It comprises hundreds of proteins with distinct roles in the rapid transcription of ribosomal RNA (rRNA) and efficient processing within units comprising a fibrillar centre and a dense fibrillar component and ribosome assembly in a granular component 1 . The precise localization of most nucleolar proteins and whether their specific localization contributes to the radial flux of pre-rRNA processing have remained unknown owing to insufficient resolution in imaging studies 2-5 . Therefore, how these nucleolar proteins are functionally coordinated with stepwise pre-rRNA processing requires further investigation. Here we screened 200 candidate nucleolar proteins using high-resolution live-cell microscopy and identified 12 proteins that are enriched towards the periphery of the dense fibrillar component (PDFC). Among these proteins, unhealthy ribosome biogenesis 1 (URB1) is a static, nucleolar protein that ensures 3' end pre-rRNA anchoring and folding for U8 small nucleolar RNA recognition and the subsequent removal of the 3' external transcribed spacer (ETS) at the dense fibrillar component-PDFC boundary. URB1 depletion leads to a disrupted PDFC, uncontrolled pre-rRNA movement, altered pre-rRNA conformation and retention of the 3' ETS. These aberrant 3' ETS-attached pre-rRNA intermediates activate exosome-dependent nucleolar surveillance, resulting in decreased 28S rRNA production, head malformations in zebrafish and delayed embryonic development in mice. This study provides insight into functional sub-nucleolar organization and identifies a physiologically essential step in rRNA maturation that requires the static protein URB1 in the phase-separated nucleolus., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Astrocytes activate and crosstalk with neurons influencing inflammatory responses following ischemic stroke. The distribution, abundance, and activity of microRNAs in astrocytes-derived exosomes after ischemic stroke remains largely unknown. In this study, exosomes were extracted from primary cultured mouse astrocytes via ultracentrifugation, and exposed to oxygen glucose deprivation/re‑oxygenation injury to mimic experimental ischemic stroke. SmallRNAs from astrocyte-derived exosomes were sequenced, and differentially expressed microRNAs were randomly selected and verified by stem-loop real time quantitative polymerase chain reaction. We found that 176 microRNAs, including 148 known and 28 novel microRNAs, were differentially expressed in astrocyte-derived exosomes following oxygen glucose deprivation/re‑oxygenation injury. In gene ontology enrichment, Kyoto encyclopedia of genes and genomes pathway analyses, and microRNA target gene prediction analyses, these alteration in microRNAs were associated to a broad spectrum of physiological functions including signaling transduction, neuroprotection and stress responses. Our findings warrant further investigating of these differentially expressed microRNAs in human diseases particularly ischemic stroke., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Understanding gene transcription and mRNA-protein (mRNP) dynamics in single cells in a multicellular organism has been challenging. The catalytically dead CRISPR-Cas13 (dCas13) system has been used to visualize RNAs in live cells without genetic manipulation. We optimize this system to track developmentally expressed mRNAs in zebrafish embryos and to understand features of endogenous transcription kinetics and mRNP export., Results: We report that zygotic microinjection of purified CRISPR-dCas13-fluorescent proteins and modified guide RNAs allows single- and dual-color tracking of developmentally expressed mRNAs in zebrafish embryos from zygotic genome activation (ZGA) until early segmentation period without genetic manipulation. Using this approach, we uncover non-synchronized de novo transcription between inter-alleles, synchronized post-mitotic re-activation in pairs of alleles, and transcriptional memory as an extrinsic noise that potentially contributes to synchronized post-mitotic re-activation. We also reveal rapid dCas13-engaged mRNP movement in the nucleus with a corralled and diffusive motion, but a wide varying range of rate-limiting mRNP export, which can be shortened by Alyref and Nxf1 overexpression., Conclusions: This optimized dCas13-based toolkit enables robust spatial-temporal tracking of endogenous mRNAs and uncovers features of transcription and mRNP motion, providing a powerful toolkit for endogenous RNA visualization in a multicellular developmental organism., (© 2023. The Author(s).)

Clayey soil seriously affects water-holding capacity and nutrient movement. Adopting appropriate agronomic measures to optimize the distribution of soil inorganic nitrogen (SIN) and reduce the nitrogen (N) loss in this soil is the key to agricultural sustainable development. To clarify the effect of deep fertilization of slow/controlled release fertilizer with sowing on N loss in a clayey soil wheat field, two types of fertilizers, conventional fertilizer (CN) and slow/controlled release fertilizer (RCU), were selected in this study. Here, we evaluated the effects of these two fertilizer types on wheat yield, seasonal N runoff loss, ammonia volatilization, and N 2 O emissions in wheat fields in two typical fertilization modes (manual surface sowing and spreading (B) and belowground fertilization of slow/controlled release urea with mechanized strip sowing (D)). The temporal and spatial distribution characteristics of SIN in topsoil were also analyzed. The results showed that under the same fertilizer type, the wheat yield of D treatment was significantly higher than that of B treatment, whereas the yield of RCU was notably higher than that of CN under the same fertilization mode. D-RCU achieved the highest yield of 6.97 t·hm -2 . The seasonal N losses from runoff and ammonia volatilization were higher than that from N 2 O emissions, and the responses of different N loss pathways to fertilizer types and fertilization methods were diverse. Fertilizer type and runoff occurrence time were the main influencing factors of N runoff loss, and N runoff loss of the RCU treatment was higher in the non-fertilization period. Unfortunately, affected by annual rainfall pattern, the seasonal N runoff loss of the RCU treatment (20.35 kg·hm -2 ) was significantly higher than that of the CN treatment (10.49 kg·hm -2 ). The late growth period was the main phase of ammonia volatilization, and the later period was jointly affected by fertilization modes and fertilizer types. The B-CN treatment induced the highest seasonal ammonia volatilization (18.15 kg·hm -2 ), which was significantly higher than that of the other treatments (7.31-8.38 kg·hm -2 ). Additionally, the D-RCU treatment (2.41 kg·hm -2 ) tended to reduce the N 2 O emissions in comparison to that in the B-CN treatment (4.02 kg·hm -2 ). The results also indicated that the horizontal movement of SIN was higher than the vertical movement. Deep fertilization of RCU was conducive to optimizing the spatial and temporal distribution of SIN, which was the main reason for the increase in wheat yield and the control of N loss from wheat fields. These results suggest that RCU is a suitable alternative fertilizer for increasing yield and reducing N loss in clayey soil wheat fields; D-RCU can increase the wheat yield and reduce ammonia volatilization and N 2 O emissions in wheat fields by optimizing the spatial and temporal distribution of SIN, and its increasing effect on N runoff loss in the non-fertilization period deserves attention.

The high incidence of mutations and the crucial roles of KAT2A in cancer development have received increased attention. Nevertheless, a systematic comparison of the heterogeneity and dynamics across different cancer types has not been conducted. Hence, a deep analysis using public databases was performed to clarify the contributions of KAT2A and its correlation with tumorigenesis. The raw data regarding KAT2A expression in cancer patients and healthy controls were obtained from The Cancer Genome Atlas (TCGA). Sexually dimorphic manner, genomic alterations, and expression pattern of KAT2A, as well as the association of the KAT2A with survival, were retrieved from UALCAN, cBioportal, and TISIDB databases. Additionally, the Protein-Protein Interaction (PPI) analysis was conducted using the STRING database. The human protein atlas was used to obtain the staining results of protein levels in cancer and normal samples. The correlation between KAT2A and its potential target drugs was determined using TISIDB and HISTome2. Compared to the normal tissues, CHOL and TGCT tumors presented significantly high KAT2A expression, which was positively correlated with BLCA, BRCA, CESC, CHOL, COAD, ESCA, HNSC, KICH, KIRP, LIHC, LUAD, LUSC, READ, STAD, and THCA. However, no significant difference was detected between normal and tumor tissues for the sex difference pattern of KAT2A expression. The PPI analysis indicated that TADA3, CCDC101, TRRAP, SUPT3H, MYC, TADA2A, and USP22 levels were positively correlated with KAT2A expression, while TADA2B and ATXN7 were negatively correlated. A positive link of KAT2A with cancer isotypes and significant connections of the KAT2A expression to poor overall and disease-free survival were also observed. Further validation was conducted using immunohistochemistry (IHC) staining, qPCR, and Western blot. Some potential HAT inhibitory drugs of KAT2A were also determined, but more work and clinical trials are required before their application.

Introduction: Alzheimer's disease (AD) is the most prevalent type of dementia and can cause abnormal cognitive function and progressive loss of essential life skills. Early screening is thus necessary for the prevention and intervention of AD. Speech dysfunction is an early onset symptom of AD patients. Recent studies have demonstrated the promise of automated acoustic assessment using acoustic or linguistic features extracted from speech. However, most previous studies have relied on manual transcription of text to extract linguistic features, which weakens the efficiency of automated assessment. The present study thus investigates the effectiveness of automatic speech recognition (ASR) in building an end-to-end automated speech analysis model for AD detection., Methods: We implemented three publicly available ASR engines and compared the classification performance using the ADReSS-IS2020 dataset. Besides, the SHapley Additive exPlanations algorithm was then used to identify critical features that contributed most to model performance., Results: Three automatic transcription tools obtained mean word error rate texts of 32%, 43%, and 40%, respectively. These automated texts achieved similar or even better results than manual texts in model performance for detecting dementia, achieving classification accuracies of 89.58%, 83.33%, and 81.25%, respectively., Conclusion: Our best model, using ensemble learning, is comparable to the state-of-the-art manual transcription-based methods, suggesting the possibility of an end-to-end medical assistance system for AD detection with ASR engines. Moreover, the critical linguistic features might provide insight into further studies on the mechanism of AD., (© 2023 S. Karger AG, Basel.)

The genetic disorder Prader-Willi syndrome (PWS) is mainly caused by the loss of multiple paternally expressed genes in chromosome 15q11-q13 (the PWS region). Early diagnosis of PWS is essential for timely treatment, leading to effectively easing some clinical symptoms. Molecular approaches for PWS diagnosis at the DNA level are available, but the diagnosis of PWS at the RNA level has been limited. Here, we show that a cluster of paternally transcribed snoRNA-ended long noncoding RNAs ( sno-lncRNAs , sno-lncRNA1-5 ) derived from the SNORD116 locus in the PWS region can serve as diagnostic markers. In particular, quantification analysis has revealed that 6,000 copies of sno-lncRNA3 are present in 1 μL whole blood samples from non-PWS individuals. sno-lncRNA 3 is absent in all examined whole blood samples of 8 PWS individuals compared to 42 non-PWS individuals and dried blood samples of 35 PWS individuals compared to 24 non-PWS individuals. Further developing a new CRISPR-MhdCas13c system for RNA detection with a sensitivity of 10 molecules per μL has ensured sno-lncRNA3 detection in non-PWS, but not PWS individuals. Together, we suggest that the absence of sno-lncRNA3 represents a potential marker for PWS diagnosis that can be detected by both RT-qPCR and CRISPR-MhdCas13c systems with only microlitre amount of blood samples. Such an RNA-based sensitive and convenient approach may facilitate the early detection of PWS.

Introduction: Chronic refractory low back pain (CRLBP) is a diagnosis characterized by chronic low back pain in patients who are poor candidates for surgery and fail conservative management. High-frequency spinal cord stimulation (HF-SCS) is a new advance in neuromodulation that may be effective in treating these patients. However, the cost burden of this therapy is yet undetermined., Materials and Methods: IBM MarketScan® (IBM, Armonk, NY) data bases were used to retrospectively identify patients with HF-SCS implantation between 2016 and 2019 in the United States. Those with low back pain diagnosis without history of surgery were included in the cohort. Cost data, including inpatient and outpatient service, medication, and out-of-pocket costs, were collected at six months before HF-SCS implantation and one, three, and six months after implantation. The explant rate within six months was evaluated., Results: A total of 119 patients met the inclusion criteria. Most patients were female (73.1%) and owned commercial insurance (83.2%). Common comorbidities included inflammatory arthritis (22.7%), depression (26.1%), hypertension (44.5%), and obesity (26.1%). In the six months before HF-SCS implantation, patients incurred median total costs of $15,766 (first quartile [Q1]: $8,847; third quartile [Q3]: $24,947), whereas the postimplant median total cost excluding device acquisition was $398 (Q1: $145, Q3: $1,272) at one month, $2,569 (Q1: $823, Q3: $5,266) at three months, and $5,840 (Q1: $2,160; Q3: $14,607) at six months. The average reduction in total cost was $6,914 (95% CI: $588, $12,458, p < 0.001). The median total acquisition cost was $43,586 (Q1: $29,506, Q3: $69,426), with most coming from outpatient services. Of 88 patients with six-month continuous enrollment, two (2.3%) had device explant., Conclusions: We present an analysis using large claims data bases of the cost of HF-SCS for treating CRLBP and show that it may be associated with a significant decrease in total health care costs, offsetting device acquisition costs in 27 months. As advances in neuromodulation expand therapy options for patients, it will be important to understand their financial implications., (Copyright © 2022 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)