Approaching the quantum limit in two-dimensional semiconductor contacts.

The development of next-generation electronics requires scaling of channel material thickness down to the two-dimensional limit while maintaining ultralow contact resistance1,2. Transition-metal dichalcogenides can sustain transistor scaling to the end of roadmap, but despite a myriad of efforts, the device performance remains contact-limited3-12. In particular, the contact resistance has not surpassed that of covalently bonded metal-semiconductor junctions owing to the intrinsic van der Waals gap, and the best contact technologies are facing stability issues3,7. Here we push the electrical contact of monolayer molybdenum disulfide close to the quantum limit by hybridization of energy bands with semi-metallic antimony ([Formula: see text]) through strong van der Waals interactions. The contacts exhibit a low contact resistance of 42 ohm micrometres and excellent stability at 125 degrees Celsius. Owing to improved contacts, short-channel molybdenum disulfide transistors show current saturation under one-volt drain bias with an on-state current of 1.23 milliamperes per micrometre, an on/off ratio over 108 and an intrinsic delay of 74 femtoseconds. These performances outperformed equivalent silicon complementary metal-oxide-semiconductor technologies and satisfied the 2028 roadmap target. We further fabricate large-area device arrays and demonstrate low variability in contact resistance, threshold voltage, subthreshold swing, on/off ratio, on-state current and transconductance13. The excellent electrical performance, stability and variability make antimony ([Formula: see text]) a promising contact technology for transition-metal-dichalcogenide-based electronics beyond silicon.

Uniform nucleation and epitaxy of bilayer molybdenum disulfide on sapphire.

Two-dimensional transition-metal dichalcogenides (TMDs) are of interest for beyond-silicon electronics1,2. It has been suggested that bilayer TMDs, which combine good electrostatic control, smaller bandgap and higher mobility than monolayers, could potentially provide improvements in the energy-delay product of transistors3-5. However, despite advances in the growth of monolayer TMDs6-14, the controlled epitaxial growth of multilayers remains a challenge15. Here we report the uniform nucleation (>99%) of bilayer molybdenum disulfide (MoS2) on c-plane sapphire. In particular, we engineer the atomic terrace height on c-plane sapphire to enable an edge-nucleation mechanism and the coalescence of MoS2 domains into continuous, centimetre-scale films. Fabricated field-effect transistor (FET) devices based on bilayer MoS2 channels show substantial improvements in mobility (up to 122.6 cm2 V-1 s-1) and variation compared with FETs based on monolayer films. Furthermore, short-channel FETs exhibit an on-state current of 1.27 mA µm-1, which exceeds the 2028 roadmap target for high-performance FETs16.

Direct mapping of bending and torsional dynamics in individual nanostructures.

Investigating coherent acoustic vibrations in nanostructured materials provides fundamental insights into optomechanical responses and microscopic energy flow. Extensive measurements of vibrational dynamics have been performed for a wide variety of nanoparticles and nanoparticle assemblies. However, virtually all of them show that only the dilation modes are launched after laser excitations, and the acoustic bending and torsional motions, which are commonly observed in photoexcited chemical bonds, are absent. Unambiguous identification and refined characterization of these "missing" modes have been a long-standing issue. In this report, we investigated the acoustic vibrational dynamics of individual Au nanoprisms on free-standing graphene substrates using an ultrafast high-sensitivity dark-field imaging approach in four-dimensional transmission electron microscopy. Following optical excitations, we observed low-frequency multiple-mode oscillations and higher superposition amplitudes at nanoprism corners and edges on the subnanoparticle level. In combination with finite-element simulations, we determined that these vibrational modes correspond to out-of-plane bending and torsional motions, superimposed by an overall tilting effect of the nanoprisms. The launch and relaxation processes of these modes are highly pertinent to substrate effects and nanoparticle geometries. These findings contribute to the fundamental understanding about acoustic dynamics of individual nanostructures and their interaction with substrates.

MRI-based tumor shrinkage patterns after early neoadjuvant therapy in breast cancer: correlation with molecular subtypes and pathological response after therapy.

BACKGROUND: MRI-based tumor shrinkage patterns (TSP) after neoadjuvant therapy (NAT) have been associated with pathological response. However, the understanding of TSP after early NAT remains limited. We aimed to analyze the relationship between TSP after early NAT and pathological response after therapy in different molecular subtypes. METHODS: We prospectively enrolled participants with invasive ductal breast cancers who received NAT and performed pretreatment DCE-MRI from September 2020 to August 2022. Early-stage MRIs were performed after the first (1st-MRI) and/or second (2nd-MRI) cycle of NAT. Tumor shrinkage patterns were categorized into four groups: concentric shrinkage, diffuse decrease (DD), decrease of intensity only (DIO), and stable disease (SD). Logistic regression analysis was performed to identify independent variables associated with pathologic complete response (pCR), and stratified analysis according to tumor hormone receptor (HR)/human epidermal growth factor receptor 2 (HER2) disease subtype. RESULTS: 344 participants (mean age: 50 years, 113/345 [33%] pCR) with 345 tumors (1 bilateral) had evaluable 1st-MRI or 2nd-MRI to comprise the primary analysis cohort, of which 244 participants with 245 tumors had evaluable 1st-MRI (82/245 [33%] pCR) and 206 participants with 207 tumors had evaluable 2nd-MRI (69/207 [33%] pCR) to comprise the 1st- and 2nd-timepoint subgroup analysis cohorts, respectively. In the primary analysis, multivariate analysis showed that early DD pattern (OR = 12.08; 95% CI 3.34-43.75; p < 0.001) predicted pCR independently of the change in tumor size (OR = 1.37; 95% CI 0.94-2.01; p = 0.106) in HR+/HER2- subtype, and the change in tumor size was a strong pCR predictor in HER2+ (OR = 1.61; 95% CI 1.22-2.13; p = 0.001) and triple-negative breast cancer (TNBC, OR = 1.61; 95% CI 1.22-2.11; p = 0.001). Compared with the change in tumor size, the SD pattern achieved a higher negative predictive value in HER2+ and TNBC. The statistical significance of complete 1st-timepoint subgroup analysis was consistent with the primary analysis. CONCLUSION: The diffuse decrease pattern in HR+/HER2- subtype and stable disease in HER2+ and TNBC after early NAT could serve as additional straightforward and comprehensible indicators of treatment response. TRIAL REGISTRATION: Trial registration at https://www.chictr.org.cn/ . REGISTRATION NUMBER: ChiCTR2000038578, registered September 24, 2020.

Molecular mechanisms of spinal cord injury repair across vertebrates: A comparative review.

In humans and other adult mammals, axon regeneration is difficult in axotomized neurons. Therefore, spinal cord injury (SCI) is a devastating event that can lead to permanent loss of locomotor and sensory functions. Moreover, the molecular mechanisms of axon regeneration in vertebrates are not very well understood, and currently, no effective treatment is available for SCI. In striking contrast to adult mammals, many nonmammalian vertebrates such as reptiles, amphibians, bony fishes and lampreys can spontaneously resume locomotion even after complete SCI. In recent years, rapid progress in the development of next-generation sequencing technologies has offered valuable information on SCI. In this review, we aimed to provide a comparison of axon regeneration process across classical model organisms, focusing on crucial genes and signalling pathways that play significant roles in the regeneration of individually identifiable descending neurons after SCI. Considering the special evolutionary location and powerful regenerative ability of lamprey and zebrafish, they will be the key model organisms for ongoing studies on spinal cord regeneration. Detailed study of SCI in these model organisms will help in the elucidation of molecular mechanisms of neuron regeneration across species.

Reciprocal relationships between stress and depressive symptoms: the essential role of the nucleus accumbens.

BACKGROUND: Stress and depression have a reciprocal relationship, but the neural underpinnings of this reciprocity are unclear. We investigated neuroimaging phenotypes that facilitate the reciprocity between stress and depressive symptoms. METHODS: In total, 22 195 participants (52.0% females) from the population-based UK Biobank study completed two visits (initial visit: 2006-2010, age = 55.0 ± 7.5 [40-70] years; second visit: 2014-2019; age = 62.7 ± 7.5 [44-80] years). Structural equation modeling was used to examine the longitudinal relationship between self-report stressful life events (SLEs) and depressive symptoms. Cross-sectional data were used to examine the overlap between neuroimaging correlates of SLEs and depressive symptoms on the second visit among 138 multimodal imaging phenotypes. RESULTS: Longitudinal data were consistent with significant bidirectional causal relationship between SLEs and depressive symptoms. In cross-sectional analyses, SLEs were significantly associated with lower bilateral nucleus accumbal volume and lower fractional anisotropy of the forceps major. Depressive symptoms were significantly associated with extensive white matter hyperintensities, thinner cortex, lower subcortical volume, and white matter microstructural deficits, mainly in corticostriatal-limbic structures. Lower bilateral nucleus accumbal volume were the only imaging phenotypes with overlapping effects of depressive symptoms and SLEs (B = -0.032 to -0.023, p = 0.006-0.034). Depressive symptoms and SLEs significantly partially mediated the effects of each other on left and right nucleus accumbens volume (proportion of effects mediated = 12.7-14.3%, p < 0.001-p = 0.008). For the left nucleus accumbens, post-hoc seed-based analysis showed lower resting-state functional connectivity with the left orbitofrontal cortex (cluster size = 83 voxels, p = 5.4 × 10-5) in participants with high v. no SLEs. CONCLUSIONS: The nucleus accumbens may play a key role in the reciprocity between stress and depressive symptoms.

USP5: Comprehensive insights into structure, function, biological and disease-related implications, and emerging therapeutic opportunities.

Ubiquitin specific protease 5 (USP5) is a vital deubiquitinating enzyme that regulates various physiological functions by removing ubiquitin chains from target proteins. This review provides an overview of the structural and functional characteristics of USP5. Additionally, we discuss the role of USP5 in regulating diverse cellular processes, including cell proliferation, apoptosis, DNA double-strand damage, methylation, heat stress, and protein quality control, by targeting different substrates. Furthermore, we describe the involvement of USP5 in several pathological conditions such as tumors, pathological pain, developmental abnormalities, inflammatory diseases, and virus infection. Finally, we introduce newly developed inhibitors of USP5. In conclusion, investigating the novel functions and substrates of USP5, elucidating the underlying mechanisms of USP5-substrate interactions, intensifying the development of inhibitors, and exploring the upstream regulatory mechanisms of USP5 in detail can provide a new theoretical basis for the treatment of various diseases, including cancer, which is a promising research direction with considerable potential. Overall, USP5 plays a critical role in regulating various physiological and pathological processes, and investigating its novel functions and regulatory mechanisms may have significant implications for the development of therapeutic strategies for cancer and other diseases.

Animal models of heart failure with preserved ejection fraction (HFpEF): from metabolic pathobiology to drug discovery.

Heart failure (HF) with preserved ejection fraction (HFpEF) is currently a preeminent challenge for cardiovascular medicine. It has a poor prognosis, increasing mortality, and is escalating in prevalence worldwide. Despite accounting for over 50% of all HF patients, the mechanistic underpinnings driving HFpEF are poorly understood, thus impeding the discovery and development of mechanism-based therapies. HFpEF is a disease syndrome driven by diverse comorbidities, including hypertension, diabetes and obesity, pulmonary hypertension, aging, and atrial fibrillation. There is a lack of high-fidelity animal models that faithfully recapitulate the HFpEF phenotype, owing primarily to the disease heterogeneity, which has hampered our understanding of the complex pathophysiology of HFpEF. This review provides an updated overview of the currently available animal models of HFpEF and discusses their characteristics from the perspective of energy metabolism. Interventional strategies for efficiently utilizing energy substrates in preclinical HFpEF models are also discussed.

SERS biosensors based on catalytic hairpin self-assembly and hybridization chain reaction cascade signal amplification strategies for ultrasensitive microRNA-21 detection.

A highly sensitive surface-enhanced Raman scattering (SERS) biosensor has been developed for the detection of microRNA-21 (miR-21) using an isothermal enzyme-free cascade amplification method involving catalytic hairpin assembly (CHA) and hybridization chain reaction (HCR). The CHA reaction is triggered by the target miR-21, which causes hairpin DNA (C1 and C2) to self-assemble into CHA products. After AgNPs@Capture captures the resulting CHA product, the HCR reaction is started, forming long-stranded DNA on the surface of AgNPs. A strong SERS signal is generated due to the presence of a large amount of the Raman reporter methylene blue (MB) in the vicinity of the SERS "hot spot" on the surface of AgNPs. The monitoring of the SERS signal changes of MB allows for the highly sensitive and specific detection of miR-21. In optimal conditions, the biosensor exhibits a satisfactory linear range and a low detection limit for miR-21 of 42.3 fM. Additionally, this SERS biosensor shows outstanding selectivity and reproducibility. The application of this methodology to clinical blood samples allows for the differentiation of cancer patients from healthy controls. As a result, the CHA-HCR amplification strategy used in this SERS biosensor could be a useful tool for miRNA detection and early cancer screening.

Association between brain similarity to severe mental illnesses and comorbid cerebral, physical, and cognitive impairments.

Severe mental illnesses (SMIs) are often associated with compromised brain health, physical comorbidities, and cognitive deficits, but it is incompletely understood whether these comorbidities are intrinsic to SMI pathophysiology or secondary to having SMIs. We tested the hypothesis that cerebral, cardiometabolic, and cognitive impairments commonly observed in SMIs can be observed in non-psychiatric individuals with SMI-like brain patterns of deviation as seen on magnetic resonance imaging. 22,883 participants free of common neuropsychiatric conditions from the UK Biobank (age = 63.4 ± 7.5 years, range = 45-82 years, 50.9% female) were split into discovery and replication samples. The regional vulnerability index (RVI) was used to quantify each participant's respective brain similarity to meta-analytical patterns of schizophrenia spectrum disorder, bipolar disorder, and major depressive disorder in gray matter thickness, subcortical gray matter volume, and white matter integrity. Cluster analysis revealed five clusters with distinct RVI profiles. Compared with a cluster with no RVI elevation, a cluster with RVI elevation across all SMIs and brain structures showed significantly higher volume of white matter hyperintensities (Cohen's d = 0.59, pFDR < 10-16), poorer cardiovascular (Cohen's d = 0.30, pFDR < 10-16) and metabolic (Cohen's d = 0.12, pFDR = 1.3 × 10-4) health, and slower speed of information processing (|Cohen's d| = 0.11-0.17, pFDR = 1.6 × 10-3-4.6 × 10-8). This cluster also had significantly higher level of C-reactive protein and alcohol use (Cohen's d = 0.11 and 0.28, pFDR = 4.1 × 10-3 and 1.1 × 10-11). Three other clusters with respective RVI elevation in gray matter thickness, subcortical gray matter volume, and white matter integrity showed intermediate level of white matter hyperintensities, cardiometabolic health, and alcohol use. Our results suggest that cerebral, physical, and cognitive impairments in SMIs may be partly intrinsic via shared pathophysiological pathways with SMI-related brain anatomical changes.

Brain deficit patterns of metabolic illnesses overlap with those for major depressive disorder: A new metric of brain metabolic disease.

Metabolic illnesses (MET) are detrimental to brain integrity and are common comorbidities in patients with mental illnesses, including major depressive disorder (MDD). We quantified effects of MET on standard regional brain morphometric measures from 3D brain MRI as well as diffusion MRI in a large sample of UK BioBank participants. The pattern of regional effect sizes of MET in non-psychiatric UKBB subjects was significantly correlated with the spatial profile of regional effects reported by the largest meta-analyses in MDD but not in bipolar disorder, schizophrenia or Alzheimer's disease. We used a regional vulnerability index (RVI) for MET (RVI-MET) to measure individual's brain similarity to the expected patterns in MET in the UK Biobank sample. Subjects with MET showed a higher effect size for RVI-MET than for any of the individual brain measures. We replicated elevation of RVI-MET in a sample of MDD participants with MET versus non-MET. RVI-MET scores were significantly correlated with the volume of white matter hyperintensities, a neurological consequence of MET and age, in both groups. Higher RVI-MET in both samples was associated with obesity, tobacco smoking and frequent alcohol use but was unrelated to antidepressant use. In summary, MET effects on the brain were regionally specific and individual similarity to the pattern was more strongly associated with MET than any regional brain structural metric. Effects of MET overlapped with the reported brain differences in MDD, likely due to higher incidence of MET, smoking and alcohol use in subjects with MDD.

Deciphering the causal relationship between blood pressure and regional white matter integrity: A two-sample Mendelian randomization study.

Elevated arterial blood pressure (BP) is a common risk factor for cerebrovascular and cardiovascular diseases, but no causal relationship has been established between BP and cerebral white matter (WM) integrity. In this study, we performed a two-sample Mendelian randomization (MR) analysis with individual-level data by defining two nonoverlapping sets of European ancestry individuals (genetics-exposure set: N = 203,111; mean age = 56.71 years, genetics-outcome set: N = 16,156; mean age = 54.61 years) from UK Biobank to evaluate the causal effects of BP on regional WM integrity, measured by fractional anisotropy of diffusion tensor imaging. Two BP traits: systolic and diastolic blood pressure were used as exposures. Genetic variant was carefully selected as instrumental variable (IV) under the MR analysis assumptions. We existing large-scale genome-wide association study summary data for validation. The main method used was a generalized version of inverse-variance weight method while other MR methods were also applied for consistent findings. Two additional MR analyses were performed to exclude the possibility of reverse causality. We found significantly negative causal effects (FDR-adjusted p < .05; every 10 mmHg increase in BP leads to a decrease in FA value by .4% ~ 2%) of BP traits on a union set of 17 WM tracts, including brain regions related to cognitive function and memory. Our study extended the previous findings of association to causation for regional WM integrity, providing insights into the pathological processes of elevated BP that might chronically alter the brain microstructure in different regions.

A delta-radiomic lymph node model using dynamic contrast enhanced MRI for the early prediction of axillary response after neoadjuvant chemotherapy in breast cancer patients.

BACKGROUND: The objective of this paper is to explore the value of a delta-radiomic model of the axillary lymph node (ALN) using dynamic contrast-enhanced (DCE) MRI for early prediction of the axillary pathological complete response (pCR) of breast cancer patients after neoadjuvant chemotherapy (NAC). METHODS: A total of 120 patients with ALN-positive breast cancer who underwent breast MRI before and after the first cycle of NAC between October 2018 and May 2021 were prospectively included in this study. Patients were divided into a training (n = 84) and validation (n = 36) cohort based on the temporal order of their treatments. Radiomic features were extracted from the largest slice of targeted ALN on DCE-MRI at pretreatment and after one cycle of NAC, and their changes (delta-) were calculated and recorded. Logistic regression was then applied to build radiomic models using the pretreatment (pre-), first-cycle(1st-), and changes (delta-) radiomic features separately. A clinical model was also built and combined with the radiomic models. The models were evaluated by discrimination, calibration, and clinical application and compared using DeLong test. RESULTS: Among the three radiomic models, the ALN delta-radiomic model performed the best with AUCs of 0.851 (95% CI: 0.770-0.932) and 0.822 (95% CI: 0.685-0.958) in the training and validation cohorts, respectively. The clinical model yielded moderate AUCs of 0.742 (95% CI: 0.637-0.846) and 0.723 (95% CI: 0.550-0.896), respectively. After combining clinical features to the delta-radiomics model, the efficacy of the combined model (AUC = 0.932) in the training cohort was significantly higher than that of both the delta-radiomic model (Delong p = 0.017) and the clinical model (Delong p < 0.001) individually. Additionally, in the validation cohort, the combined model had the highest AUC (0.859) of any of the models we tested although this was not statistically different from any other individual model's validation AUC. Calibration and decision curves showed a good agreement and a high clinical benefit for the combined model. CONCLUSION: This preliminary study indicates that ALN-based delta-radiomic model combined with clinical features is a promising strategy for the early prediction of downstaging ALN status after NAC. Future axillary MRI applications need to be further explored.

Time Course Changes of Synthetic Relaxation Time During Neoadjuvant Chemotherapy in Breast Cancer: The Optimal Parameter for Treatment Response Evaluation.

BACKGROUND: Synthetic MRI (syMRI) has enabled quantification of multiple relaxation parameters (T1/T2 relaxation time [T1/T2], proton density [PD]), and their longitudinal change during neoadjuvant chemotherapy (NAC) promises to be valuable parameters for treatment response evaluation in breast cancer. PURPOSE: To investigate the time course changes of syMRI parameters during NAC and evaluate their value as predictors for pathological complete response (pCR) in breast cancer. STUDY TYPE: Retrospective, longitudinal. POPULATION: A total of 129 women (median age, 50 years; range, 28-69 years) with locally advanced breast cancer who underwent NAC; all performed multiple conventional breast MRI examinations with added syMRI during NAC. FIELD STRENGTH/SEQUENCE: A 3.0 T, T1-weighted dynamic contrast enhanced and syMRI acquired by a multiple-dynamic, multiple-echo sequence. ASSESSMENT: Breast MRI was set at four time-points: baseline, after one cycle, after three or four cycles of NAC and preoperation. SyMRI parameters and tumor diameters were measured and their changes from baseline were calculated. All parameters were compared between pCR and non-pCR. Interaction between syMRI parameters and clinicopathological features was analyzed. STATISTICAL TESTS: Mann-Whitney U tests, random effects model of repeated measurement, receiver operating characteristic (ROC) analysis, interaction analysis. RESULTS: Median synthetic T1/T2/PD and tumor diameter generally decreased throughout NAC. Absolute T1 at early-NAC, T1, and PD at mid-NAC were significantly lower in the pCR group. After early-NAC, the T1 change was significantly higher in the pCR (median ± IQR, 18.17 ± 11.33) than the non-pCR group (median ± IQR, 10.90 ± 10.03), with the highest area under the ROC curves (AUC) of 0.769 (95% CI, 0.684-0.838). Interaction analysis showed that histological grade III patients had higher odds ratio (OR) (OR = 1.206) compared to grade II patients (OR = 1.067). DATA CONCLUSION: Synthetic T1 changes after one cycle of NAC maybe useful for early evaluating NAC response in breast cancer during whole treatment cycles. However, its discriminative ability is significantly affected by histological grade. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

Potential Antihuman Epidermal Growth Factor Receptor 2 Target Therapy Beneficiaries: The Role of MRI-Based Radiomics in Distinguishing Human Epidermal Growth Factor Receptor 2-Low Status of Breast Cancer.

BACKGROUND: Multiparametric MRI radiomics could distinguish human epidermal growth factor receptor 2 (HER2)-positive from HER2-negative breast cancers. However, its value for further distinguishing HER2-low from HER2-negative breast cancers has not been investigated. PURPOSE: To investigate whether multiparametric MRI-based radiomics can distinguish HER2-positive from HER2-negative breast cancers (task 1) and HER2-low from HER2-negative breast cancers (task 2). STUDY TYPE: Retrospective. POPULATION: Task 1: 310 operable breast cancer patients from center 1 (97 HER2-positive and 213 HER2-negative); task 2: 213 HER2-negative patients (108 HER2-low and 105 HER2-zero); 59 patients from center 2 (16 HER2-positive, 27 HER2-low and 16 HER2-zero) for external validation. FIELD STRENGTH/SEQUENCE: A 3.0 T/T1-weighted contrast-enhanced imaging (T1CE), diffusion-weighted imaging (DWI)-derived apparent diffusion coefficient (ADC). ASSESSMENT: Patients in center 1 were assigned to a training and internal validation cohort at a 2:1 ratio. Intratumoral and peritumoral features were extracted from T1CE and ADC. After dimensionality reduction, the radiomics signatures (RS) of two tasks were developed using features from T1CE (RS-T1CE), ADC (RS-ADC) alone and T1CE + ADC combination (RS-Com). STATISTICAL TESTS: Mann-Whitney U tests, the least absolute shrinkage and selection operator, receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). RESULTS: For task 1, RS-ADC yielded higher area under the ROC curve (AUC) in the training, internal, and external validation of 0.767/0.725/0.746 than RS-T1CE (AUC = 0.733/0.674/0.641). For task 2, RS-T1CE yielded higher AUC of 0.765/0.755/0.678 than RS-ADC (AUC = 0.706/0.608/0.630). For both of task 1 and task 2, RS-Com achieved the best performance with AUC of 0.793/0.778/0.760 and 0.820/0.776/0.711, respectively, and obtained higher clinical benefit in DCA compared with RS-T1CE and RS-ADC. The calibration curves of all RS demonstrated a good fitness. DATA CONCLUSION: Multiparametric MRI radiomics could noninvasively and robustly distinguish HER2-positive from HER2-negative breast cancers and further distinguish HER2-low from HER2-negative breast cancers. EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 2.

Frontal white matter association with sleep quality and the role of stress.

An important measure of brain health is the integrity of white matter connectivity structures that link brain regions. Studies have found an association between poorer sleep quality and decreased white matter integrity. Stress is among the strongest predictors of sleep quality. This study aimed to evaluate the association between sleep quality and white matter and to test if the relationship persisted after accounting for stress. White matter microstructures were measured by diffusion tensor imaging in a population of Old Order Amish/Mennonite (N = 240). Sleep quality was determined by the Pittsburgh Sleep Quality Index. Current stress levels were measured by the perceived stress scale. Exposure to lifetime stress was measured by the lifetime stressor inventory. Microstructures of four white matter tracts: left and right anterior limbs of internal capsule, left anterior corona radiata, and genu of corpus callosum were significantly correlated with sleep quality (all p ≤ 0.001). The current stress level was a significant predictor of sleep quality (p ≤ 0.001) while lifetime stress was not. PSQI remained significantly associated with white matter integrity in these frontal tracts (all p < 0.01) after accounting for current stress and lifetime stress, while current and lifetime stress were not significant predictors of white matter in any of the four models. Sleep quality did not have any substantial mediation role between stress and white matter integrity. Sleep quality was significantly associated with several frontal white matter tracts that connect brain structures important for sleep regulation regardless of current or past stress levels.

Three-dimensional visualization and evaluation of hilar cholangiocarcinoma resectability and proposal of a new classification.

BACKGROUND: As digital medicine has exerted profound influences upon diagnosis and treatment of hepatobiliary diseases, our study aims to investigate the accuracy of three-dimensional visualization and evaluation (3DVE) system in assessing the resectability of hilar cholangiocarcinoma (hCCA), and explores its potential clinical value. MATERIALS AND METHODS: The discovery cohort, containing 111 patients from April 2013 to December 2019, was retrospectively included to determine resectability according to revised criteria for unresectability of hCCA. 3D visualization models were reconstructed to evaluate resectability parameters including biliary infiltration, vascular involvement, hepatic atrophy and metastasis. Evaluation accuracy were compared between contrast-enhanced CT and 3DVE. Logistic analysis was performed to identify independent risk factors of R0 resection. A new comprehensive 3DVE classification of hCCA based on factors influencing resectability was proposed to investigate its role in predicting R0 resection and prognosis. The main outcomes were also analyzed in cohort validation, including 34 patients from January 2020 to August 2022. RESULTS: 3DVE showed an accuracy rate of 91% (95%CI 83.6-95.4%) in preoperatively evaluating hCCA resectability, significantly higher than 81% (95%CI 72.8-87.7%) of that of CT (p = 0.03). By multivariable analysis, hepatic artery involvement in 3DVE was identified an independent risk factor for R1 or R2 resection (OR = 3.5, 95%CI 1.4,8.8, P < 0.01). New 3DVE hCCA classification was valuable in predicting patients' R0 resection rate (p < 0.001) and prognosis (p < 0.0001). The main outcomes were internally validated. CONCLUSIONS: 3DVE exhibited a better efficacy in evaluating hCCA resectability, compared with contrast-enhanced CT. Preoperative 3DVE demonstrated hepatic artery involvement was an independent risk factor for the absence of R0 margin. 3DVE classification of hCCA was valuable in clinical practice.

Mass spectrometry imaging technology in metabolomics: A systematic review.

Mass spectrometry imaging (MSI) is a powerful label-free analysis technique that can provide simultaneous spatial distribution of multiple compounds in a single experiment. By combining the sensitive and rapid screening of high-throughput MS with spatial chemical information, metabolite analysis and morphological characteristics are presented in a single image. MSI can be used for qualitative and quantitative analysis of metabolic profiles and it can provide visual analysis of spatial distribution information of complex biological and microbial systems. Matrix-assisted laser desorption ionization, laser ablation electrospray ionization and desorption electrospray ionization are commonly used in MSI. Here, we summarize and compare these three technologies, as well as the applications and prospects of MSI in metabolomics.

Preoperative low-molecular weight heparin chemoprophylaxis in head and neck free flap reconstruction.

BACKGROUND: The safety of presurgical thromboprophylaxis using low molecular weight heparin (LMWH) has not been well described in head and neck oncologic surgery with free tissue transfer (HNS-FTT). METHODS: Retrospective chart review of HNS-FTT patients receiving versus not receiving presurgical subcutaneous enoxaparin (Px-LMWH) was performed. Outcomes included estimated blood loss (EBL), hematoma, flap compromise, DVT or pulmonary embolus (PE). Fisher's exact test and Wilcoxon Rank Sum test were performed to compare groups. Odds ratios and associated 95 % confidence intervals were provided as appropriate. RESULTS: 43 of 128 patients (34 %) received Px-LMWH. There was no significant difference in EBL, hematoma, or flap complications between groups. Patients without Px-LMWH had higher rates of DVT and PE, although the difference did not reach statistical significance (p = 1.00, 0.095, respectively). CONCLUSION: Presurgical Px-LMWH can be used in major head and neck reconstructive surgery without increased intraoperative blood loss or postoperative complications. Larger studies will need to be done to determine the impact of Px-LMWH on DVT and PE in this patient population.

Marginal donor liver versus standard donor liver: A single-center observational study.

BACKGROUND: The effectiveness and safety of marginal donor livers remain controversial. This study aimed to investigate the clinical efficacy of marginal donor livers in patients with liver transplantation (LT). METHODS: This study included 199 liver donors (including 16 split donors) and 206 liver recipients from January 1, 2018 to January 27, 2020, with case follow-up until July 31, 2021. Clinical data of donors and recipients were retrospectively analyzed and were divided into the marginal donor and standard donor groups according to the criteria of marginal donor livers. Indices of liver and kidney functions, complications, and survival curves of the two groups were compared. RESULTS: Compared with the standard donor group, the blood creatinine levels were significantly higher in the marginal donor group in the first week after operation (P < 0.05); there were no significant differences in alanine aminotransferase, aspartate aminotransferase, and total bilirubin levels after LT (all P > 0.05); there was no significant difference in the incidence of complications after LT (P > 0.05); there was also no significant difference in the survival curve (P = 0.335). CONCLUSIONS: There were no significant differences in liver and kidney function and survival curve between the standard donor and marginal donor groups. The marginal donor liver appears safe and reliable for LT and may be an important strategy to expand the donor pool and solve the shortage of organs.