Merged magnetic resonance and light sheet microscopy of the whole mouse brain.

We have developed workflows to align 3D magnetic resonance histology (MRH) of the mouse brain with light sheet microscopy (LSM) and 3D delineations of the same specimen. We start with MRH of the brain in the skull with gradient echo and diffusion tensor imaging (DTI) at 15 µm isotropic resolution which is ~ 1,000 times higher than that of most preclinical MRI. Connectomes are generated with superresolution tract density images of ~5 µm. Brains are cleared, stained for selected proteins, and imaged by LSM at 1.8 µm/pixel. LSM data are registered into the reference MRH space with labels derived from the ABA common coordinate framework. The result is a high-dimensional integrated volume with registration (HiDiver) with alignment precision better than 50 µm. Throughput is sufficiently high that HiDiver is being used in quantitative studies of the impact of gene variants and aging on mouse brain cytoarchitecture and connectomics.

Achieving Ideal and Environmentally Stable n-Type Charge Transport in Polymer Field-Effect Transistors.

Realizing ideal charge transport in field-effect transistors (FETs) of conjugated polymers is crucial for evaluating device performance, such as carrier mobility and practical applications of conjugated polymers. However, the current FETs using conjugated polymers as the active layers generally show certain non-ideal transport characteristics and poor stability. Here, ideal charge transport of n-type polymer FETs is achieved on flexible polyimide substrates by using an organic-inorganic hybrid double-layer dielectric. Deposited conjugated polymer films show highly ordered structures and low disorder, which are supported by grazing-incidence wide-angle X-ray scattering, near-edge X-ray absorption fine structure, and molecular dynamics simulations. Furthermore, the organic-inorganic hybrid double-layer dielectric provides low interfacial defects, leading to excellent charge transport in FETs with high electron mobility (1.49 ± 0.46 cm2 V-1 s-1) and ideal reliability factors (102 ± 7%). Fabricated polymer FETs show a self-encapsulation effect, resulting in high stability of the FET charge transport. The polymer FETs still work with high mobility above 1 cm2 V-1 s-1 after storage in air for more than 300 days. Compared with state-of-the-art conjugated polymer FETs, this work simultaneously achieves ideal charge transport and environmental stability in n-type polymer FETs, facilitating rapid device optimization of high-performance polymer electronics.

Maternal and Infant Dietary Patterns Are Not Related to Food Allergy Risk in Singapore Children: GUSTO Cohort Study.

BACKGROUND: We previously reported that delayed allergenic food introduction in infancy did not increase food allergy risk until age 4 y within our prospective cohort. However, it remains unclear whether other aspects of maternal or infant diet play roles in the development of childhood food allergy. OBJECTIVES: We examined the relationship between maternal pregnancy and infant dietary patterns and the development of food allergies until age 8 y. METHODS: Among 1152 Singapore Growing Up in Singapore Towards healthy Outcomes study mother-infant dyads, the infant's diet was ascertained using food frequency questionnaires at 18 mo. Maternal dietary patterns during pregnancy were derived from 24-h diet recalls. Food allergy was determined through interviewer-administered questionnaires at regular time points from infancy to age 8 y and defined as a positive history of allergic reactions, alongside skin prick tests at 18 mo, 3, 5, and 8 y. RESULTS: Food allergy prevalence was 2.5% (22/883) at 12 mo and generally decreased over time by 8 y (1.9%; 14/736). Higher maternal dietary quality was associated with increased risk of food allergy (P ≤ 0.016); however, odds ratios were modest. Offspring food allergy risk ≤8 y showed no associations with measures of infant diet including timing of solids/food introduction (adjusted odds ratio [aOR]: 0.90; 95% confidence interval [CI]: 0.42, 1.92), infant's diet quality (aOR: 0.93; 95% CI: 0.88, 0.99) or diet diversity (aOR: 0.84; 95% CI: 0.6, 1.19). Most infants (89%) were first introduced to cow milk protein within the first month of life, while egg and peanut introduction were delayed (58.3% introduced by mean age 8.8 mo and 59.8% by mean age 18.1 mo, respectively). CONCLUSIONS: Apart from maternal diet quality showing a modest association, infant's allergenic food introduction, diet quality, and dietary diversity were not associated with food allergy development in this Asian pediatric population. Interventional studies are needed to evaluate the efficacy of these approaches to food allergy prevention across different populations.

The Association between Migration and Prevalence of Allergic Diseases: A Systematic Review and Meta-Analysis.

INTRODUCTION: Allergic diseases remain of concern due to their increasing prevalence worldwide. Intrinsic and environmental risk factors have been implicated in the pathogenesis of allergic disease. Among the possible risk factors, migration has been associated with the manifestation of allergic diseases. We aimed to consolidate the existing evidence, review the hypotheses for the relationship between environmental factors and allergic disease, and provide a direction for future work. METHODS: This systematic review and meta-analysis complied with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The Web of Science database was searched in September 2023 to retrieve publications investigating the relationship between allergic rhinitis (AR), atopic dermatitis (AD), or asthma and the following factors: (i) migrant status (i.e., migrants vs. natives) or (ii) duration since migration among migrants. Risk of bias was assessed using the JBI critical appraisal tool. Details and findings from the included studies were also summarized and meta-analyses were conducted where appropriate. RESULTS: Fifty studies encompassing an estimated 3,755,248 individuals were reviewed. Articles investigated asthma (n = 46), AR (n = 16), and AD (n = 14). A variety of migration-related factors were also studied: movement of individuals across regions (n = 40), duration since immigration (n = 12), age at immigration (n = 9), and acculturation (n = 2). Migration status was not significantly associated with AD (pooled odds ratio [pOR] = 0.68, 95% confidence interval (CI) = 0.31, 1.49). Although AR prevalence was lower among immigrants than natives (pOR = 0.58, 95% CI = 0.45, 0.74), immigrants who had resided at least 10 years in the destination country had a higher risk of AR than immigrants with a duration of residence of less than 10 years (pOR = 8.36, 95% CI = 4.15, 16.81). Being an immigrant was also associated with a decreased risk of asthma (pOR = 0.56, 95% CI = 0.44, 0.72). Among immigrants, residing in the host country for at least 10 years was associated with increased asthma manifestation (pOR = 1.85, 95% CI = 1.25, 2.73). Immigrants who migrated aged 5 and below did not exhibit a significantly higher likelihood of asthma than migrants who immigrated older than 5 years (pOR = 1.01, 95% CI = 0.68, 1.50). CONCLUSION: This review was limited by the primarily cross-sectional nature of the included studies. Objective diagnoses of allergic disease, such as using the spirometry of bronchodilator reversibility test for asthma rather than questionnaire responses, could add to the reliability of the outcomes. Furthermore, immigrant groups were mostly nonspecific, with little distinction between their country of origin. Overall, migration appears to be a protective factor for allergic diseases, but the protection subsides over time and the prevalence of allergic diseases among the immigrant group approaches that of the host population.

Transcriptome analysis identifies an ASD-Like phenotype in oligodendrocytes and microglia from C58/J amygdala that is dependent on sex and sociability.

BACKGROUND: Autism Spectrum Disorder (ASD) is a group of neurodevelopmental disorders with higher incidence in males and is characterized by atypical verbal/nonverbal communication, restricted interests that can be accompanied by repetitive behavior, and disturbances in social behavior. This study investigated brain mechanisms that contribute to sociability deficits and sex differences in an ASD animal model. METHODS: Sociability was measured in C58/J and C57BL/6J mice using the 3-chamber social choice test. Bulk RNA-Seq and snRNA-Seq identified transcriptional changes in C58/J and C57BL/6J amygdala within which DMRseq was used to measure differentially methylated regions in amygdala. RESULTS: C58/J mice displayed divergent social strata in the 3-chamber test. Transcriptional and pathway signatures revealed immune-related biological processes differ between C58/J and C57BL/6J amygdala. Hypermethylated and hypomethylated genes were identified in C58/J versus C57BL/6J amygdala. snRNA-Seq data in C58/J amygdala identified differential transcriptional signatures within oligodendrocytes and microglia characterized by increased ASD risk gene expression and predicted impaired myelination that was dependent on sex and sociability. RNA velocity, gene regulatory network, and cell communication analysis showed diminished oligodendrocyte/microglia differentiation. Findings were verified using Bulk RNA-Seq and demonstrated oxytocin's beneficial effects on myelin gene expression. LIMITATIONS: Our findings are significant. However, limitations can be noted. The cellular mechanisms linking reduced oligodendrocyte differentiation and reduced myelination to an ASD phenotype in C58/J mice need further investigation. Additional snRNA-Seq and spatial studies would determine if effects in oligodendrocytes/microglia are unique to amygdala or if this occurs in other brain regions. Oxytocin's effects need further examination to understand its' potential as an ASD therapeutic. CONCLUSIONS: Our work demonstrates the C58/J mouse model's utility in evaluating the influence of sex and sociability on the transcriptome in concomitant brain regions involved in ASD. Our single-nucleus transcriptome analysis elucidates potential pathological roles of oligodendrocytes and microglia in ASD. This investigation provides details regarding regulatory features disrupted in these cell types, including transcriptional gene dysregulation, aberrant cell differentiation, altered gene regulatory networks, and changes to key pathways that promote microglia/oligodendrocyte differentiation. Our studies provide insight into interactions between genetic risk and epigenetic processes associated with divergent affiliative behavior and lack of positive sociability.

A novel image deep learning-based sub-centimeter pulmonary nodule management algorithm to expedite resection of the malignant and avoid over-diagnosis of the benign.

OBJECTIVES: With the popularization of chest computed tomography (CT) screening, there are more sub-centimeter (≤ 1 cm) pulmonary nodules (SCPNs) requiring further diagnostic workup. This area represents an important opportunity to optimize the SCPN management algorithm avoiding "one-size fits all" approach. One critical problem is how to learn the discriminative multi-view characteristics and the unique context of each SCPN. METHODS: Here, we propose a multi-view coupled self-attention module (MVCS) to capture the global spatial context of the CT image through modeling the association order of space and dimension. Compared with existing self-attention methods, MVCS uses less memory consumption and computational complexity, unearths dimension correlations that previous methods have not found, and is easy to integrate with other frameworks. RESULTS: In total, a public dataset LUNA16 from LIDC-IDRI, 1319 SCPNs from 1069 patients presenting to a major referral center, and 160 SCPNs from 137 patients from three other major centers were analyzed to pre-train, train, and validate the model. Experimental results showed that performance outperforms the state-of-the-art models in terms of accuracy and stability and is comparable to that of human experts in classifying precancerous lesions and invasive adenocarcinoma. We also provide a fusion MVCS network (MVCSN) by combining the CT image with the clinical characteristics and radiographic features of patients. CONCLUSION: This tool may ultimately aid in expediting resection of the malignant SCPNs and avoid over-diagnosis of the benign ones, resulting in improved management outcomes. CLINICAL RELEVANCE STATEMENT: In the diagnosis of sub-centimeter lung adenocarcinoma, fusion MVCSN can help doctors improve work efficiency and guide their treatment decisions to a certain extent. KEY POINTS: • Advances in computed tomography (CT) not only increase the number of nodules detected, but also the nodules that are identified are smaller, such as sub-centimeter pulmonary nodules (SCPNs). • We propose a multi-view coupled self-attention module (MVCS), which could model spatial and dimensional correlations sequentially for learning global spatial contexts, which is better than other attention mechanisms. • MVCS uses fewer huge memory consumption and computational complexity than the existing self-attention methods when dealing with 3D medical image data. Additionally, it reaches promising accuracy for SCPNs' malignancy evaluation and has lower training cost than other models.

Novel STAT3 oligonucleotide compounds suppress tumor growth and overcome the acquired resistance to sorafenib in hepatocellular carcinoma.

Signal transducer and activator of transcription 3 (STAT3) plays an important role in the occurrence and progression of tumors, leading to resistance and poor prognosis. Activation of STAT3 signaling is frequently detected in hepatocellular carcinoma (HCC), but potent and less toxic STAT3 inhibitors have not been discovered. Here, based on antisense technology, we designed a series of stabilized modified antisense oligonucleotides targeting STAT3 mRNA (STAT3 ASOs). Treatment with STAT3 ASOs decreased the STAT3 mRNA and protein levels in HCC cells. STAT3 ASOs significantly inhibited the proliferation, survival, migration, and invasion of cancer cells by specifically perturbing STAT3 signaling. Treatment with STAT3 ASOs decreased the tumor burden in an HCC xenograft model. Moreover, aberrant STAT3 signaling activation is one of multiple signaling pathways involved in sorafenib resistance in HCC. STAT3 ASOs effectively sensitized resistant HCC cell lines to sorafenib in vitro and improved the inhibitory potency of sorafenib in a resistant HCC xenograft model. The developed STAT3 ASOs enrich the tools capable of targeting STAT3 and modulating STAT3 activity, serve as a promising strategy for treating HCC and other STAT3-addicted tumors, and alleviate the acquired resistance to sorafenib in HCC patients. A series of novel STAT3 antisense oligonucleotide were designed and showed potent anti-cancer efficacy in hepatocellular carcinoma in vitro and in vivo by targeting STAT3 signaling. Moreover, the selected STAT3 ASOs enhance sorafenib sensitivity in resistant cell model and xenograft model.

Burgers, Fast Foods, and Increased Associated Risk for Atopic Dermatitis: A Cross-Sectional Study of Dietary Habits among Young Chinese Adults in Singapore/Malaysia.

BACKGROUND: We see increasing evidence that dietary and nutrients factors play a pivotal role in allergic diseases and recent global findings suggest that dietary habits influence the pathogenesis of atopic dermatitis (AD). Frequent consumption of fast food diets is associated with AD development. Despite the rising prevalence of AD in Asia, efforts in investigating the role of dietary habits and AD in adults are still lacking. METHODS: We evaluated the association between the dietary intake of 16 food types and AD manifestations using our Singapore/Malaysia Cross-sectional Genetics Epidemiology Study (SMCGES) population. Dietary habits profiles of 11,494 young Chinese adults (1,550 AD cases/2,978 non-atopic controls/6,386 atopic controls) were assessed by an investigator-administered questionnaire. AD cases were further evaluated for their chronicity (550 chronic) and severity (628 moderate-to-severe). Additionally, we derived a novel food index, Quality of Diet based on Glycaemic Index Score (QDGIS), to examine the association between dietary intake of glycaemic index (GI) and various AD phenotypes. RESULTS: The majority of AD subjects are distributed in the good (37.1%) and moderate (36.2%) QDGIS classes. From the multivariable analyses for age and gender, a moderate QDGIS class was significantly associated with a lower odds of AD (adjusted odds ratio (AOR): 0.844; 95% confidence interval (CI): 0.719-0.991; p < 0.05) and moderate-to-severe AD (AOR: 0.839; 95% CI: 0.714-0.985; p < 0.05). A good QDGIS class was only significantly associated with a lower odds of chronic AD (AOR: 0.769; 95% CI: 0.606-0.976; p < 0.05). Among high GI foods, frequent consumption of burgers/fast food was strongly associated with an increased risk of chronic and moderate-to-severe AD. Among low GI foods, increased intake frequencies of fruits, vegetables, and pulses decreased the odds of AD. Finally, we identified significant associations between frequent seafood, margarine, butter, and pasta consumption with an increased odds of AD despite them having little GI values. CONCLUSION: While genetic components are well-established in their risks associated with increased AD prevalence, there is still a lack of a focus epidemiology study associating dietary influence with AD. Based on the first allergic epidemiology study conducted here in Singapore and Malaysia, it laid the groundwork to guide potential dietary interventions from changing personal dietary habits.

Resiliency process in the family after childhood leukaemia diagnosis: A longitudinal qualitative study.

AIMS: To construct a conceptual framework on the process of family resilience during the first year following childhood leukaemia diagnosis. DESIGN: A longitudinal qualitative interview study. METHODS: A longitudinal qualitative study following a grounded theory methodology was employed. Semi-structured interviews were conducted with parents of children with leukaemia in a general hospital. The participants were recruited through purposive and theoretical sampling and longitudinal engagement was achieved by conducting interviews at 1, 3, 6, and 12 months after the leukaemia diagnosis. The core category and categories were saturated following the enrolment of parents of children with leukaemia. Data collection and analyses were performed simultaneously. RESULTS: Sixteen parents of children with leukaemia participated. The core category of 'families living with childhood leukaemia' refers to the process of family resilience during the first year following childhood leukaemia diagnosis, which includes three phases: (1) destruction and resiliency period; (2) adjustment and consolidation period; and (3) growth and planning period. CONCLUSION: This study explored the dynamic, complex and continuous processes of resilience among families coping with childhood leukaemia during the first year following diagnosis. Further research should design tailored family interventions that characterise the different phases of family resilience, aiming to support family well-being, integrity and functioning. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: Both families and healthcare professionals must create an enabling environment that supports families coping with difficulties. Understanding the different phases of family resilience allows healthcare professionals to provide holistic care that meets the demands of families with childhood leukaemia. IMPACT: Unique knowledge emerged about the family's resiliency process when facing childhood leukaemia, suggesting a family-led revolution in understanding and managing childhood leukaemia. Therefore, the development of phased, resilience-based family interventions is imperative. REPORTING METHOD: This study was reported using the COREQ checklist. PATIENT OR PUBLIC CONTRIBUTION: Patients contributed via study participation.

Simultaneous Dual-Wavelength Source Raman Spectroscopy with a Handheld Confocal Probe for Analysis of the Chemical Composition of In Vivo Human Skin.

Confocal Raman spectroscopy (CRS) is a powerful tool that has been widely used for biological tissue analysis because of its noninvasive nature, high specificity, and rich biochemical information. However, current commercial CRS systems suffer from limited detection regions (450-1750 cm-1), bulky sizes, nonflexibilities, slow acquisitions by consecutive excitations, and high costs if using a Fourier transform (FT) Raman spectroscopy with an InGaAs detector, which impede their adoption in clinics. In this study, we developed a portable CRS system with a simultaneous dual-wavelength source and a miniaturized handheld probe (120 mm × 60 mm × 50 mm) that can acquire spectra in both fingerprint (FP, 450-1750 cm-1) and high wavenumber (HW, 2800-3800 cm-1) regions simultaneously. An innovative design combining 671 and 785 nm lasers for simultaneous excitation through a compact and high-efficiency (>90%) wavelength combiner was implemented. Moreover, to decouple the fused FP and HW spectra, a first-of-its-kind precise Raman spectra separation algorithm (PRSSA) was developed based on the maximum a posteriori probability (MAP) estimate. The accuracy of spectra separation was greater than 99%, demonstrated in both phantom experiments and in vivo human skin measurements. The total data acquisition time was reduced by greater than 50% compared to other CRS systems. The results proved our proposed CRS system and PRSSA's superior capability in fast and ultrawideband spectra acquisition will significantly improve the integration of CRS in the clinical workflow.

Expression Changes in Programmed Death Ligand 1 from Precancerous Lesions to Invasive Adenocarcinoma in Subcentimeter Pulmonary Nodules: A Large Study of 2022 Cases in China.

PURPOSE: This large-scale, multicenter, retrospective observational study aimed to evaluate the clinicopathological and molecular profiles associated with programmed death-ligand 1 (PD-L1) expression in precancerous lesions and invasive adenocarcinoma in subcentimeter pulmonary nodules. PATIENTS AND METHODS: Patients with histologically confirmed atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (ADC) were included. PD-L1 expression was evaluated at each center using a PD-L1 immunohistochemistry 22C3 pharmDx kit (Agilent, Santa Clara, CA, USA). The tumor proportion score (TPS) cutoff values were set at ≥ 1% and ≥ 50%. RESULTS: A total of 2022 nodules from 1844 patients were analyzed. Of these, 9 (0.45%) nodules had PD-L1 TPS ≥ 50%, 187 (9.25%) had PD-L1 TPS 1-49%, and 1826 (90.30%) had PD-L1 TPS < 1%. A total of 378 (18.69%), 1016 (50.25%), and 628 (31.06%) nodules were diagnosed as AAH/AIS, MIA, and ADC, respectively, by pathology. A total of 1377 (68.10%), 591 (25.67%), and 54 (2.67%) nodules were diagnosed as pure ground-glass opacity (GGO), mixed GGO, and solid nodules, respectively, by computed tomography. There was a significant difference between PD-L1 expression and anaplastic lymphoma kinase (ALK) mutation status (P < 0.001). PD-L1 expression levels were significantly different from those determined using the International Association for the Study of Lung Cancer (IASLC) grading system (P < 0.001). CONCLUSIONS: PD-L1 expression was significantly associated with radiological and pathological invasiveness and driver mutation status in subcentimeter pulmonary nodules. The significance of PD-L1 expression in the evolution of early-stage lung adenocarcinoma requires further investigation.

High-throughput doubly-encoded single-pixel spectrometer with an extended aperture.

Infrared devices are increasingly used in industrial, medical, and environmental monitoring applications. Cost-effectiveness, robustness, and portability are characteristics that are highly sought after and they can be enabled by a dispersive spectrometer carrying a single-pixel detector. In this paper, we demonstrate a novel, high-throughput dispersive spectrometer that has its spectral resolution decoupled from its throughput. The proposed spectrometer implements a two-stage Hadamard transform encoding process that allows significantly more light into the system to enhance its signal-to-noise ratio. As a single-pixel detector is used to collect the spectral information, the proposed system can be easily implemented in other desired wavelengths. Furthermore, we develop a method to remove the need for uniform illumination at the entrance aperture by taking into consideration its spatial information during the reconstruction process, thereby increasing the ease of the design of devices required for in situ measurement.

TDI-like multi-slit hyperspectral imaging for enhanced throughput via the Kalman filter.

The time-delay integration (TDI) technique is increasingly used to improve the signal-to-noise ratio (SNR) of remote sensing and imaging by exposing the scene multiple times. Inspired by the principle of TDI, we propose a TDI-like pushbroom multi-slit hyperspectral imaging (MSHSI) approach. In our system, multiple slits are used to significantly improve the throughput of the system, thereby enhancing the sensitivity and SNR through multiple exposures of the same scene during pushbroom scan. Meanwhile, a linear dynamic model for the pushbroom MSHSI is established, where the Kalman filter (KF) is employed to reconstruct the time-varying overlapped spectral images on a single conventional image sensor. Further, we designed and fabricated a customized optical system that can operate in both multi-slit and single slit modes to experimentally verify the feasibility of the proposed method. Experimental results indicate that the developed system improved SNR by a factor of about 7 compared to that of the single slit mode, while demonstrating excellent resolution in both spatial and spectral dimensions.

Integrating multimodality magnetic resonance imaging to the Allen Mouse Brain Common Coordinate Framework.

High-resolution magnetic resonance imaging (MRI) affords unique image contrasts to nondestructively probe the tissue microstructure; validation of MRI findings with conventional histology is essential to better understand the MRI contrasts. However, the dramatic difference in the spatial resolution and image contrast of these two techniques impedes accurate comparison between MRI metrics and traditional histology. To better validate various MRI metrics, we acquired whole mouse brain multigradient recalled-echo and multishell diffusion MRI datasets at 25-µm isotropic resolution. The recently developed Allen Mouse Brain Common Coordinate Framework (CCFv3) provides opportunities to integrate multimodal and multiscale datasets of the whole mouse brain in a common three-dimensional (3D) space. The T2*, quantitative susceptibility mapping, diffusion tensor imaging, and neurite orientation dispersion and density imaging parameters were compared with both serial two-photon tomography images and 3D Nissl staining images in the CCFv3 at the same spatial resolution. The correlation between MRI and Nissl staining strongly depends on different metrics and different regions of the brain. Integrating different imaging modalities to the same space may substantially improve our understanding of the complexity of the brain at different scales.

Prenatal heroin exposure alters brain morphology and connectivity in adolescent mice.

The United States is experiencing a dramatic increase in maternal opioid misuse and, consequently, the number of individuals exposed to opioids in utero. Prenatal opioid exposure has both acute and long-lasting effects on health and wellbeing. Effects on the brain, often identified at school age, manifest as cognitive impairment, attention deficit, and reduced scholastic achievement. The neurobiological basis for these effects is poorly understood. Here, we examine how in utero exposure to heroin affects brain development into early adolescence in a mouse model. Pregnant C57BL/6J mice received escalating doses of heroin twice daily on gestational days 4-18. The brains of offspring were assessed on postnatal day 28 using 9.4 T diffusion MRI of postmortem specimens at 36 µm resolution. Whole-brain volumes and the volumes of 166 bilateral regions were compared between heroin-exposed and control offspring. We identified a reduction in whole-brain volume in heroin-exposed offspring and heroin-associated volume changes in 29 regions after standardizing for whole-brain volume. Regions with bilaterally reduced standardized volumes in heroin-exposed offspring relative to controls include the ectorhinal and insular cortices. Regions with bilaterally increased standardized volumes in heroin-exposed offspring relative to controls include the periaqueductal gray, septal region, striatum, and hypothalamus. Leveraging microscopic resolution diffusion tensor imaging and precise regional parcellation, we generated whole-brain structural MRI diffusion connectomes. Using a dimension reduction approach with multivariate analysis of variance to assess group differences in the connectome, we found that in utero heroin exposure altered structure-based connectivity of the left septal region and the region that acts as a hub for limbic regulatory actions. Consistent with clinical evidence, our findings suggest that prenatal opioid exposure may have effects on brain morphology, connectivity, and, consequently, function that persist into adolescence. This work expands our understanding of the risks associated with opioid misuse during pregnancy and identifies biomarkers that may facilitate diagnosis and treatment.

Extended Magnetic Reconnection in Kinetic Plasma Turbulence.

Magnetic reconnection and plasma turbulence are ubiquitous processes important for laboratory, space, and astrophysical plasmas. Reconnection has been suggested to play an important role in the energetics and dynamics of turbulence by observations, simulations, and theory for two decades. The fundamental properties of reconnection at kinetic scales, essential to understanding the general problem of reconnection in magnetized turbulence, remain largely unknown at present. Here, we present an application of the magnetic flux transport method that can accurately identify reconnection in turbulence to a three-dimensional simulation. Contrary to ideas that reconnection in turbulence would be patchy and unpredictable, highly extended reconnection X lines, on the same order of magnitude as the system size, form at kinetic scales. Extended X lines develop through bidirectional reconnection spreading. They satisfy critical balance characteristic of turbulence, which predicts the X-line extent at a given scale. These results present a picture of fundamentally extended reconnection in kinetic-scale turbulence.

Porphyromonas gingivalis predicts local recurrence after endoscopic submucosal dissection of early esophageal squamous cell carcinoma or precancerous lesion.

BACKGROUND: Porphyromonas gingivalis plays an oncogenic role in development and progression of esophageal squamous cell carcinoma (ESCC). However, the impact of P. gingivalis on local recurrence of early ESCC or precancerous lesion after ESD treatment remains unknown. The present study aimed to evaluate the impact of P. gingivalis on local recurrence after ESD treatment of early ESCC or high-grade dysplasia (HGD). METHODS: The amount of P. gingivalis was assessed by immunohistochemistry in 205 patients with early ESCC or HGD. Univariate and multivariate Cox regression analyses were performed to determine the effect of P. gingivalis on local recurrence. Propensity score matching analysis was performed to reduce the imbalance of baseline characteristics. A nomogram integrating significant prognostic factors was built for local recurrence prediction. RESULTS: The amount of P. gingivalis increased significantly in neoplasms that invaded up to muscularis mucosa and submucosa compared with lesions confined to epithelium or lamina propria. Overabundance of P. gingivalis was positively associated with invasion depth, post-ESD stricture and local recurrence. Univariate and multivariate Cox regression analyses revealed that P. gingivalis, longitudinal length of lesion and lymphovascular invasion were independent predictors for post-ESD recurrence. A nomogram comprising P. gingivalis, lymphovascular involvement, and lesion length performed well for prediction of post-ESD local recurrence with the concordance indices of 0.72 (95%CI, 0.62 to 0.80), 0.72 (95%CI, 0.63 to 0.80), and 0.74 (95%CI, 0.65 to 0.83) in the validation cohort, the entire cohort, and the subcohort after PSM, respectively. CONCLUSION: P. gingivalis overabundance is a risk factor and a potential predictor for local recurrence of early ESCC or HGD after ESD treatment. Thus, clearance of P. gingivalis represents an attractive strategy for prognosis improvement and for prevention of ESCC.

Porphyromonas gingivalis promotes progression of esophageal squamous cell cancer via TGFß-dependent Smad/YAP/TAZ signaling.

Microbial dysbiosis in the upper digestive tract is linked to an increased risk of esophageal squamous cell carcinoma (ESCC). Overabundance of Porphyromonas gingivalis is associated with shorter survival of ESCC patients. We investigated the molecular mechanisms driving aggressive progression of ESCC by P. gingivalis. Intracellular invasion of P. gingivalis potentiated proliferation, migration, invasion, and metastasis abilities of ESCC cells via transforming growth factor-ß (TGFß)-dependent Drosophila mothers against decapentaplegic homologs (Smads)/Yes-associated protein (YAP)/Transcriptional coactivator with PDZ-binding motif (TAZ) activation. Smads/YAP/TAZ/TEA domain transcription factor1 (TEAD1) complex formation was essential to initiate downstream target gene expression, inducing an epithelial-mesenchymal transition (EMT) and stemness features. Furthermore, P. gingivalis augmented secretion and bioactivity of TGFß through glycoprotein A repetitions predominant (GARP) up-regulation. Accordingly, disruption of either the GARP/TGFß axis or its activated Smads/YAP/TAZ complex abrogated the tumor-promoting role of P. gingivalis. P. gingivalis signature genes based on its activated effector molecules can efficiently distinguish ESCC patients into low- and high-risk groups. Targeting P. gingivalis or its activated effectors may provide novel insights into clinical management of ESCC.

Latencies to the first interictal epileptiform discharges recorded by the electroencephalography in different epileptic patients.

PURPOSE: Interictal epileptiform discharges (IEDs) captured in electroencephalography (EEG) have a high diagnostic value for epileptic patients. Extending the recording time may increase the possibility of obtaining IEDs. The purpose of our research was to determine how long it took for various epileptic individuals to receive their first IEDs. METHODS: We retrospectively analyzed patients who were diagnosed with epilepsy and had no anti-seizure medications (ASMs) between September 2018 and March 2019 in the neurology department of the First Affiliated Hospital of Xi'an Jiaotong University. Each individual underwent a 24-h long-term video electroencephalographic monitoring (VEM) procedure. Clinical information including age, gender, age of seizure onset, frequency of seizures, the interval between last seizure and VEM, and results of neuroimaging were gathered. We also calculated the times from the start of the VEM to the first definite IEDs. RESULTS: A total of 241 patients were examined, including 191 with focal-onset epilepsy and 50 with generalized epilepsy. In individuals with focal-onset epilepsy, the median latency to the first IED was 63.0 min (IQR 19.0-299.0 min), as compared to 30.0 min (IQR 12.5-62.0 min) in patients with generalized epilepsy (p < 0.001). The latency to the first IED is significantly related to the age of seizure onset (HR = 0.988, p = 0.049), the interval between last seizure and VEM (HR = 0.998, p = 0.013). But it is not correlated with seizure frequency, gender and age. CONCLUSIONS: IEDs were discovered during 24-h EEG monitoring in 222/241(92.1%) of the epilepsy patients that were included. Compared to focal-onset epilepsy, generalized epilepsy demonstrated a much shorter latency to IED. Patients with late-onset epilepsy or those without recent episodes may require longer EEG monitoring periods.

Resting-state electroencephalography microstate dynamics altered in patients with migraine with and without aura-A pilot study.

OBJECTIVE: To evaluate electroencephalography (EEG) microstate differences between patients with migraine with aura (MWA), patients with migraine without aura (MWoA), and healthy controls (HC). BACKGROUND: Previous research employing microstate analysis found unique microstate alterations in patients with MWoA; however, it is uncertain how microstates appear in patients with MWA. METHODS: This study was conducted at the Headache Clinic of the First Affiliated Hospital of Xi'an Jiaotong University. In total, 30 patients with MWA, 30 with MWoA, and 30 HC were enrolled in this cross-sectional study. An EEG was recorded for all participants under resting state. The microstate parameters of four widely recognized microstate classes A-D were calculated and compared across the three groups. RESULTS: The occurrence of microstate B (MsB) in the MWoA group was significantly higher than in the HC (p = 0.006, Cohen's d = 0.72) and MWA (p = 0.016, Cohen's d = 0.57) groups, while the contribution of MsB was significantly increased in the MWoA group compared to the HC group (p = 0.016, Cohen's d = 0.64). Microstate A (MsA) displayed a longer duration in the MWA group compared to the MWoA group (p = 0.007, Cohen's d = 0.69). Furthermore, the transition probability between MsB and microstate D was significantly increased in the MWoA group compared to the HC group (p = 0.009, Cohen's d = 0.68 for B to D; p = 0.007, Cohen's d = 0.71 for D to B). Finally, the occurrence and contribution of MsB were positively related to headache characteristics in the MWoA group but negatively in the MWA group, whereas the duration of MsA was positively related to the visual analog scale in the MWA group (all p < 0.05). CONCLUSIONS: Patients with MWA and MWoA have altered microstate dynamics, indicating that resting-state brain network disorders may play a role in migraine pathogenesis. Microstate parameters may have the potential to aid clinical management, which needs to be investigated further.