Evaluating the value of 18F-PSMA-1007 PET/CT in the detection and identification of prostate cancer using histopathology as the standard.

BACKGROUND: Prostate-specific membrane antigen (PSMA) PET/CT is a highly regarded radionuclide imaging modality for prostate cancer (PCa). This study aimed to evaluate the diagnostic performance of 18F-PSMA-1007 PET/CT in detecting intraprostatic lesions of PCa using radical prostatectomy (RP) specimens as a reference standard and to establish an optimal maximum standardized uptake value (SUVmax) cutoff for distinguishing between PCa and non-PCa lesions. METHODS: We retrospectively collected 117 patients who underwent 18F-PSMA-1007 PET/CT before RP. The uptake of the index tumor and contralateral non-PCa lesion was assessed. Histopathology of RP specimens was used as the gold standard. Kappa test was used to evaluate the consistency of preoperative PSMA PET/CT staging and postoperative pathological staging. Finally, an SUVmax cutoff value was identified by receiver operating characteristic (ROC) curve analysis to distinguish PCa lesions from non-PCa lesions. A prospective cohort including 76 patients was used to validate the results. RESULTS: The detection rate of 18F-PSMA-1007 PET/CT for prostate cancer was 96.6% (113/117). 18F-PSMA-1007 had a sensitivity of 91.2% and a positive predictive value (PPV) of 89.8% for the identification of intraprostatic lesions. The consistency test (Kappa = 0.305) indicated poor agreement between the pathologic T-stage and PSMA PET/CT T-stage. Based on ROC curve analysis, the appropriate SUVmax to diagnose PCa lesions was 8.3 (sensitivity of 71.3% and specificity 96.8%) with an area under the curve (AUC) of 0.93 (P < 0.001). This SUVmax cutoff discriminated PCa lesions from non-PCa lesions with a sensitivity of 74.4%, a specificity of 95.8% in the prospective validation group. CONCLUSIONS: 18F-PSMA-1007 PET/CT demonstrated excellent performance in detecting PCa. An optimal SUVmax threshold (8.3) could be utilized to identify lesions of PCa by 18F-PSMA-1007 PET/CT. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04521894, Registered: August 17, 2020.

Soil legacy nutrients contribute to the decreasing stoichiometric ratio of N and P loading from the Mississippi River Basin.

Human-induced nitrogen-phosphorus (N, P) imbalance in terrestrial ecosystems can lead to disproportionate N and P loading to aquatic ecosystems, subsequently shifting the elemental ratio in estuaries and coastal oceans and impacting both the structure and functioning of aquatic ecosystems. The N:P ratio of nutrient loading to the Gulf of Mexico from the Mississippi River Basin increased before the late 1980s driven by the enhanced usage of N fertilizer over P fertilizer, whereafter the N:P loading ratio started to decrease although the N:P ratio of fertilizer application did not exhibit a similar trend. Here, we hypothesize that different release rates of soil legacy nutrients might contribute to the decreasing N:P loading ratio. Our study used a data-model integration framework to evaluate N and P dynamics and the potential for long-term accumulation or release of internal soil nutrient legacy stores to alter the ratio of N and P transported down the rivers. We show that the longer residence time of P in terrestrial ecosystems results in a much slower release of P to coastal oceans than N. If contemporary nutrient sources were reduced or suspended, P loading sustained by soil legacy P would decrease much slower than that of N, causing a decrease in the N and P loading ratio. The longer residence time of P in terrestrial ecosystems and the increasingly important role of soil legacy nutrients as a loading source may explain the decreasing N:P loading ratio in the Mississippi River Basin. Our study underscores a promising prospect for N loading control and the urgency to integrate soil P legacy into sustainable nutrient management strategies for aquatic ecosystem health and water security.

Impact of non-regional lymph node metastases accurately revealed on 18F-PSMA-1007 PET/CT in the clinical management of metastatic hormone-sensitive prostate cancer.

BACKGROUND: Non-regional lymph node (NRLN) metastases has shown increasing importance in the prognosis evaluation and clinical management of primary metastatic hormone-sensitive prostate cancer (mHSPC). Hence, this study aimed to investigate the concordance rates between 18F-PSMA-1007 PET/CT and conventional imaging (CI) in revealing NRLN metastases, and explore the impact of NRLN metastases on the management of primary mHSPC. METHODS: The medical records of 224 patients with primary mHSPC were retrospectively reviewed, including 101 patients (45.1%) only received CI for TNM classification, 24 patients (10.7%) only received 18F-PSMA-1007 PET/CT, and 99 patients (44.2%) received both 18F-PSMA-1007 PET/CT and CI. Among patients who received 18F-PSMA-1007 PET/CT and CI before initial treatment, the concordance rates between 18F-PSMA-1007 PET/CT and CI were analyzed. The high-volume disease was defined as the presence of visceral metastases and/or ≥ 4 bone metastases (≥ 1 beyond the vertebral bodies or the pelvis) based on the findings of 18F-PSMA-1007 PET/CT and/or CI. The primary endpoint was progression-free survival (PFS), and Cox regression analyses were performed to explore independent predictors of PFS. RESULTS: A total of 99 patients (44.2%) received both 18F-PSMA-1007 PET/CT and CI, the concordance rate in revealing NRLN metastases between 18F-PSMA-1007 PET/CT and CI was only 61.62%, and Cohen's kappa coefficient was as low as 0.092. Moreover, 18F-PSMA-1007 PET/CT detected an additional 37 of 94 (39.4%) patients with positive NRLNs who were negative on CI. Cox regression revealed that androgen deprivation therapy (ADT), N1, high-volume, NRLN and visceral metastases were associated with worse PFS (all P < 0.05) in 224 patients. Furthermore, in patients with low-volume disease, the median PFS of patients with NRLN metastases was significantly shorter than that of patients without NRLN metastases (19.5 vs. 27.5 months, P = 0.01), while the difference between patients with low-volume plus NRLN metastases and high-volume disease was not significant (19.5 vs. 16.9 months, P = 0.55). Moreover, early docetaxel chemotherapy significantly prolonged the PFS of these patients compared with ADT alone (20.7 vs. 12.3 months, P = 0.008). CONCLUSION: NRLN metastases could be accurately revealed by 18F-PSMA-1007 PET/CT, which should be considered a high-volume feature, especially concomitant with bone metastases. Furthermore, patients with low-volume plus NRLN metastases may be suitable for more intensive treatment, such as early docetaxel chemotherapy.

The prognostic value of 18F-PSMA-1007 PET/CT in predicting pathological upgrading of newly diagnosed prostate cancer from systematic biopsy to radical prostatectomy.

Objective: This study aimed to evaluate predictors for upgrading of newly diagnosed prostate cancer from systematic biopsy (SB) to radical prostatectomy (RP) using fluorine-18 prostate-specific membrane antigen 1007 (18F-PSMA-1007) positron emission tomography/computed tomography (PET/CT) and association with clinical parameters. Materials and methods: We retrospectively collected data from biopsy-confirmed prostate cancer (PCa) patients who underwent 18F-PSMA-1007 PET/CT prior to RP from July 2019 and October 2022. Imaging characteristics derived from 18F-PSMA-1007 PET/CT and clinical parameters were compared in patients of pathological upgrading and concordance subgroups. Univariable and multivariable logistic regressions were performed to analyze factors predicting histopathological upgrading from SB to RP specimens. Discrimination ability of independent predictors was further evaluated by receiver operating characteristic (ROC) analysis with corresponding area under the curve (AUC). Results: Pathological upgrading occurred in 26.97% (41/152) PCa patients, and 23.03% (35/152) of all patients experienced pathological downgrading. Concordance rate reached 50% (76/152). International Society of Urological Pathology grade group (ISUP GG) 1(77.78%) and ISUP GG 2 (65.22%) biopsies were related with the highest rate of upgrading. Multivariable logistic regression analyses showed that prostate volume (OR= 0.933; 95% CI, 0.887-0.982; p = 0.008), ISUP GG 1 vs. 4 (OR= 13.856; 95% CI: 2.467-77.831; p = 0.003), and total uptake of PSMA-avid lesions (PSMA-TL) (OR = 1.003; 95% CI, 1.000-1.006; p = 0.029) were found to be independent risk factors of pathological upgrading after RP. The AUCs and corresponding sensitivity and specificity of the independent predictors of synthesis for upgrading were 0.839, 78.00%, and 83.30% respectively, which showed good discrimination capacity. Conclusion: 18F-PSMA-1007 PET/CT may help to predict pathological upgrading between biopsy and RP specimens, particularly for ISUP GG 1 and ISUP GG 2 patients with higher PSMA-TL and smaller prostate volume.

Plastic responses lead to increased neurotoxin production in the diatom Pseudo-nitzschia under ocean warming and acidification.

Ocean warming (OW) and acidification (OA) are recognized as two major climatic conditions influencing phytoplankton growth and nutritional or toxin content. However, there is limited knowledge on the responses of harmful algal bloom species that produce toxins. Here, the study provides quantitative and mechanistic understanding of the acclimation and adaptation responses of the domoic acid (DA) producing diatom Pseudo-nitzschia multiseries to rising temperature and pCO2 using both a one-year in situ bulk culture experiment, and an 800-day laboratory acclimation experiment. Ocean warming showed larger selective effects on growth and DA metabolism than ocean acidification. In a bulk culture experiment, increasing temperature +4 °C above ambient seawater temperature significantly increased DA concentration by up to 11-fold. In laboratory when the long-term warming acclimated samples were assayed under low temperatures, changes in growth rates and DA concentrations indicated that P. multiseries did not adapt to elevated temperature, but could instead rapidly and reversibly acclimate to temperature shifts. However, the warming-acclimated lines showed evidence of adaptation to elevated temperatures in the transcriptome data. Here the core gene expression was not reversed when warming-acclimated lines were moved back to the low temperature environment, which suggested that P. multiseries cells might adapt to rising temperature over longer timescales. The distinct strategies of phenotypic plasticity to rising temperature and pCO2 demonstrate a strong acclimation capacity for this bloom-forming toxic diatom in the future ocean.

Evaluation of a radiomics nomogram derived from Fluoride-18 PSMA-1007 PET/CT for risk stratification in newly diagnosed prostate cancer.

Objective: The aim of this study was to evaluate the performance of Fluoride-18 (18F)-PSMA-1007-PET/CT radiomics for the tumor malignancy and clinical risk stratification in primary prostate cancer (PCa). Materials and Methods: A total of 161 pathological proven PCa patients in a single center were retrospectively analyzed. Prostate-specific antigen (PSA), Gleason Score (GS) and PET/CT indexes (SUVmin, SUVmax, and SUVmean) were compared according to risk stratification. Radiomics features were extracted from PCa 18F-PSMA-1007-PET/CT imaging. The radiomics score integrating all selected parameters and clinicopathologic characteristics was used to construct a binary logistic regression and nomogram classifier. Predictors contained in the individualized prediction nomogram included radiomics score, PSA level and metastasis status. Results: The radiomics signature, which consisted of 30 selected features, was significantly associated with PSA level and Gleason score (P < 0.001 for both primary and validation cohorts). Predictors contained in the individualized prediction nomogram included radiomics score, PSA level and metastasis status. The model showed good discrimination with an area under the ROC curve of 0.719 for the GS. Combined clinical-radiomic score nomogram had a similar benefit to utilizing the PET/CT radiomic features alone for GS discrimination. Conclusion: The 18F-PSMA-1007-PET/CT radiomics signature can be used to facilitate preoperative individualized prediction of GS; incorporating the radiomics signature, PSA level, and metastasis status had similar benefits to those of utilizing the PET/CT radiomics features alone.

The 18F-PSMA-1007 PET/CT performance on metastasis status and therapy assessment in oligo-metastasis prostate cancer.

Objective: The prostate-specific membrane antigen (PSMA) PET/CT is potentially identifying patients with oligo-metastasis who would be deemed to only have localized disease in the traditional approaches. However, the best selected oligo-metastasis prostate cancer (PCa) patients most likely to benefit from system androgen deprivation therapy (ADT) are still unknown. The aim of this study was to explore the potential 18F-PSMA-1007 PET/CT parameters and clinicopathologic characteristics for oligo-metastasis PCa discrimination and follow-up evaluation. Materials and methods: A total of 180 retrospective patients with different metastasis burdens (PCa of none-metastases, oligo-metastases, and poly-metastases), different metastasis status (untreated and recurrent oligo-metastases), and follow-up ADT were included respectively. A one-way analysis of variance was used to evaluate whether PET/CT parameters and clinicopathologic characteristics were different and univariate/multivariate logistic regression models were applied to assess independent predictors in the metastasis burdens group (89/180). Selected predictors were further compared between different metastasis statuses to test the diagnostic accuracy (69/180). The predictor efficiency was evaluated by the ROC and the cut-off value was used to test the ADT response-to-treatment with a longitudinal cohort (22/180) from untreated baseline to 3-15 months. Results: The significant group differences were observed on SUVmax (P = 0.012), International Society of Urologic Pathologists (ISUP, P<0.001) and Gleason Score (P<0.001). Poly-Metastases patients had higher SUVmax, ISUP and Gleason Score compared to Non-Metastases and Oligo-Metastases patients, respectively (P<0.05, all), and no difference between Non-Metastases and Oligo-Metastases. The SUVmax, ISUP and Gleason Score were independent predictors for metastasis burdens discrimination. The untreated and recurrent oligo-metastases lesions SUVmax were also different (P = 0.036). The AUC of ROC for oligo-metastasis prediction was 0.658 (P = 0.039) when the primary prostatic carcinoma focus SUVmax was higher than 28.22, ADT response-to-treatment patients (5/5 in 22) were all progress in a follow-up test. Conclusion: The SUVmax can discriminate PCa metastasis degree and oligo-metastasis status. The ADT-treated oligo-metastasis patient may still have disease progression when the primary prostatic carcinoma focus SUVmax is greater than 28.22.

Neural Processing Differences of Facial Emotions Between Human and Vehicles: Evidence From an Event-Related Potential Study.

Vehicle "faces" are a crucial factor influencing consumer intention to purchase gasoline and electric vehicles. However, little empirical evidence has demonstrated whether people process a vehicle's face similarly to a human's face. We investigated the neural processing relationship among human facial emotions and facial emotions of gasoline and electric vehicles using a 2 (emotional) × 3 (face type) repeated measures design and electroencephalograph (EEG) recordings. The results showed that human faces appear to share a partly similar neural processing mechanism in the latency of 100-300 ms, and that both human and vehicle faces elicited the ERP components N170, EPN, and P2. The large EPN and P2 suggest that gasoline vehicle facial emotions can be perceived more efficiently than those of electric vehicles. These findings provide an insight for vehicle designers to better understand the facial emotions presented by cars.

Relieving the water-energy nexus pressure through whole supply chain management: Evidence from the provincial-level analysis in China.

Water-energy nexus (WEN) is an international hot-spot issue, while more attentions have been paid to the direct nexus effect resulting from production activities. In this context, this study firstly used the multiregional input-output (MRIO) analysis to offer a full spectrum of water and energy usage throughout the whole supply chain in China, considering production-based perspective and betweenness-based and consumption-based perspectives. And then the principal components analysis (PCA) was applied to further target the critical WEN sectors in Chinese's 30 provinces. The results show that: (1) For most of these provinces, the direct WEN pressure caused by production activities can be found in several traditional resource-intensive sectors, especially in S22 (Production and supply of electric power and steam) and S14 (Smelting and pressing of metals). (2) The most critical transmission sectors with WEN pressure was S12 (Manufacture of chemicals and chemical products), followed by S14 in most of these province. S22 was the key transmission center in several provinces, and S7 (Manufacture of textile) in Fujian and Hubei and S10 (Papermaking and printing) in Zhejiang and Hainan should also be highly-concerned. (3) For all of these provinces, the indirect WEN pressure driven by final consumption appeared in S24 (Construction industry). In addition, S16 (Manufacture of general and special-purpose machinery) and S17 (Manufacture of Transport equipment) were the other two key consumption-based WEN sectors in some provinces. Overall, the WEN pressures in Jiangsu were relatively great in China, and S12 in Hubei was the only sector facing great WEN pressure from all three perspectives. Our results can draw implications for regional sustainable development in China.

18F-PSMA-1007 PET/CT Performance on Risk Stratification Discrimination and Distant Metastases Prediction in Newly Diagnosed Prostate Cancer.

OBJECTIVE: To evaluate the prediction performance of 18F-PSMA-1007 PET/CT and clinicopathologic characteristics on prostate cancer (PCa) risk stratification and distant metastatic prediction. MATERIALS AND METHODS: A retrospective analysis was performed on 101 consecutively patients with biopsy or radical prostatectomy proved PCa who underwent 18F-PSMA-1007 PET/CT. The semi-quantitative analysis provided minimum, maximum and mean standardized uptake (SUVmin, SUVmax and SUVmean) of PCa. Association between clinicopathologic characteristics (total prostate-specific antigen, tPSA and Gleason Score, GS) and PET/CT indexes were analyzed. The diagnostic performance of distant metastatic on PET/CT parameters, tPSA and GS was evaluated using logistic regression analyses. A path analysis was conducted to evaluate the mediating effect of tPSA level on the relation between semi-quantitative parameters of primary tumors and metastatic lesions. RESULTS: The PET/CT parameters were all higher in high risk stratification subgroups (tPSA>20 ng/mL, GS ≥ 8, and tPSA>20 ng/mL and/or GS ≥ 8, respectively) with high sensitivity (86.89%, 90.16% and 83.61%, respectively). The SUVmax, tPSA and GS could effectively predict distant metastatic with high sensitivity of SUVmax (90.50%) compared with tPSA (57.14%) and GS (55.61%). With a cutoff value of 29.01ng/mL for tPSA, the detection rate of distant metastasis between low and high prediction tPSA group had statistical differences (50.00% vs. 76.60%, respectively; P = 0.006) which was not found on guideline tPSA level (P>0.05). 6/15 (40%) patients tPSA between 20ng/mL to 29.01ng/mL without distant metastases may change the risk stratification. Finally, tPSA had a partial mediating effect on SUVmax of primary tumors and metastases lesions. CONCLUSION: The 18F-PSMA-1007 PET/CT SUVmax has a higher sensitivity and can be an "imaging biomarker" for primary PCa risk stratification. The prediction tPSA level (29.01 ng/mL) is more conducive to the assessment of distant metastasis and avoid unnecessary biopsy.

Accelerated Brain Aging in Mild Traumatic Brain Injury: Longitudinal Pattern Recognition with White Matter Integrity.

Mild traumatic brain injury (mTBI) initiating long-term effects on white matter integrity resembles brain-aging changes, implying an aging process accelerated by mTBI. This longitudinal study aims to investigate the mTBI-induced acceleration of the brain-aging process by developing a neuroimaging model to predict brain age. The brain-age prediction model was defined using relevance vector regression based on fractional anisotropy from diffusion tensor imaging of 523 healthy individuals. The model was used to estimate the brain-predicted age difference (brain-PAD) between the chronological and estimated brain age in 116 acute mTBI patients and 63 healthy controls. Fifty patients were followed for 6 ∼ 12 months to evaluate the longitudinal changes in brain-PAD. We investigated whether brain-PAD was greater in patients of older age, post-concussion complaints, and apolipoprotein E (APOE) ɛ4 genotype, and whether it had the potential to predict neuropsychological outcomes. The brain-age prediction model predicted brain age accurately (r = 0.96). The brains of mTBI patients in the acute phase were estimated to be "older," with greater brain-PAD (2.59 ± 5.97 years) than the healthy controls (0.12 ± 3.19 years) (p < 0.05), and remained stable 6-12 month post-injury (2.50 ± 4.54 years). Patients who were older or who had post-concussion complaints, rather than APOE ɛ4 genotype, had greater brain-PADs (p < 0.001, p = 0.024). Additionally, brain-PAD in the acute phase predicted information processing speed at the 6 ∼ 12 month follow-up (r = -0.36, p = 0.01). In conclusion, mTBI accelerates the brain-aging process, and brain-PAD may be capable of evaluating aging-associated issues post-injury, such as increased risks of neurodegeneration.

Energy Strategy for Sustainable Development of Rural Areas Based on the Analysis of Sustainable Digital Economy.

Technology has played a vital role in modifying the lifestyle of individuals and the emerging countries are progressing so fast as no one has ever thought before. With the progression of technology boosting, the pattern of energy resources consumption has also been the center of attention for researchers in this decade. China has been one of those countries that have adopted such energy strategies in its industrial regime. The economists and information technology (IT) working together have done wonders in digitalizing and sustaining the economies that will lead to sustainable development goals. This study has been an effort to understand the role of technology and the availability of affordable energy resources in obtaining a sustainable digital economy with the mediating role of sustainable development. The population of this study was IT professionals and economists. The survey data were collected from 285 respondents selected based on purposive sampling. The software adopted for data analysis was SmartPLS 3.3.3. This study showed that technology utilization had been an important predictor of sustainable development, contributing to a sustainable digital economy. Similarly, low operational cost also moderated the relationship of sustainable development and sustainable digital economy that has been the major focus of developing countries. Moreover, the strategy of cutting down the operation costs to bring it down to the level of affordability is a major challenge for the economies such as China that have been among the low production cost. Studies on the sustainable digital economy with respect to technological use are very limited. Hence, this study will find many advantages for economists and IT professionals in the future with respect to devising the strategies taking into account the sustainable development goals and the achievement of a sustainable digital economy.

Single Mild Traumatic Brain Injury Deteriorates Progressive Interhemispheric Functional and Structural Connectivity.

The present study examined dynamic interhemispheric structural and functional connectivity in mild traumatic brain injury (mTBI) patients with longitudinal observations from early subacute to chronic stages within 1 year of injury. Forty-two mTBI patients and 42 matched healthy controls underwent clinical and neuropsychological evaluations, diffusion tensor imaging, and resting-state functional magnetic resonance imaging. All mTBI patients were initially evaluated within 14 d post-injury (T-1) and at 3 months (T-2) and 6-12 months (T-3) follow-ups. Separate transcallosal fiber tracts in the corpus callosum (CC) with respect to their specific interhemispheric cortical projections were derived with fiber tracking and voxel-mirrored homotopic connectivity analyses. With diffusion tensor imaging-based tractography, five vertical segments of the CC (I-V) were distinguished. Correlation analyses were performed to evaluate relationships between structural and functional imaging measures as well as imaging indices and neuropsychological measures. The loss of integrity in the CC demonstrated saliently persistent and time-dependent regional specificity after mTBI. The impairment spanned multiple segments from CC II at T-1 and CC I, II, VI, and V at T-2 to all subregions at T-3. Moreover, loss of interhemispheric structural connectivity through the CC corresponded well to regions presenting altered interhemispheric functional connectivity. Decreased functional connectivity in the dorsolateral prefrontal cortex thereafter contributed to poor executive function in mTBI patients. The current study provides further evidence that the CC is a sign to interhemispheric highways underpinning the widespread cerebral pathology typifying mTBI syndrome.

Corpus callosum integrity loss predicts cognitive impairment in Leukoaraiosis.

OBJECTIVE: To investigate regional white matter fibers loss in Leukoaraiosis (LA) and its relationship with cognitive impairments. METHODS: Fifty-six participants with LA and 38 healthy controls underwent clinical evaluations and MR scans. Participants with LA were classified as cognitively normal (LA-NC, n = 18), vascular cognitive impairment of none dementia (LA-VCIND, n = 24), and vascular dementia (LA-VaD, n = 14) by Mini-Mental State Examination and Clinical Dementia Rating. Cognitive domains including visual-spatial, naming, attention, language, abstraction, memory, and orientation were assessed. With the use of Tract-based spatial statistics, mean fractional anisotropy (FA) of major white matter fiber tracts were compared between LA and controls and among LA groups with varying levels of cognitive impairments. Regression analyses were performed to evaluate relationships between FA values and cognitive performance. RESULTS: Participants showed significant FA reduction in the corpus callosum (CC), bilateral corona radiata, anterior limb of the internal capsule, external capsule, posterior thalamic radiation, and superior longitudinal fasciculus compared to controls and across LA groups. The LA-VaD group showed consistent damage in the body and genu of CC compared to the LA-NC and LA-VCIND groups. A positive correlation between visual-spatial and FA reduction in right anterior corona radiates in LA-VCIND and body of CC in LA- VaD. INTERPRETATION: We found regional fiber loss in the CC across the cognitive spectrum in patients with LA and correlations between FA and visuospatial impairment in the anterior corona radiata in patients with LA-VCIND and in the body of CC in patients with LA-VaD.

Rainfall manipulation experiments as simulated by terrestrial biosphere models: Where do we stand?

Changes in rainfall amounts and patterns have been observed and are expected to continue in the near future with potentially significant ecological and societal consequences. Modelling vegetation responses to changes in rainfall is thus crucial to project water and carbon cycles in the future. In this study, we present the results of a new model-data intercomparison project, where we tested the ability of 10 terrestrial biosphere models to reproduce the observed sensitivity of ecosystem productivity to rainfall changes at 10 sites across the globe, in nine of which, rainfall exclusion and/or irrigation experiments had been performed. The key results are as follows: (a) Inter-model variation is generally large and model agreement varies with timescales. In severely water-limited sites, models only agree on the interannual variability of evapotranspiration and to a smaller extent on gross primary productivity. In more mesic sites, model agreement for both water and carbon fluxes is typically higher on fine (daily-monthly) timescales and reduces on longer (seasonal-annual) scales. (b) Models on average overestimate the relationship between ecosystem productivity and mean rainfall amounts across sites (in space) and have a low capacity in reproducing the temporal (interannual) sensitivity of vegetation productivity to annual rainfall at a given site, even though observation uncertainty is comparable to inter-model variability. (c) Most models reproduced the sign of the observed patterns in productivity changes in rainfall manipulation experiments but had a low capacity in reproducing the observed magnitude of productivity changes. Models better reproduced the observed productivity responses due to rainfall exclusion than addition. (d) All models attribute ecosystem productivity changes to the intensity of vegetation stress and peak leaf area, whereas the impact of the change in growing season length is negligible. The relative contribution of the peak leaf area and vegetation stress intensity was highly variable among models.

The effect of white matter signal abnormalities on default mode network connectivity in mild cognitive impairment.

Regions within the default mode network (DMN) are particularly vulnerable to Alzheimer's disease pathology and mechanisms of DMN disruption in mild cognitive impairment (MCI) are still unclear. White matter lesions are presumed to be mechanistically linked to vascular dysfunction whereas cortical atrophy may be related to neurodegeneration. We examined associations between DMN seed-based connectivity, white matter lesion load, and cortical atrophy in MCI and cognitively healthy controls. MCI showed decreased functional connectivity (FC) between the precuneus-seed and bilateral lateral temporal cortex (LTC), medial prefrontal cortex (mPFC), posterior cingulate cortex, and inferior parietal lobe compared to those with controls. When controlling for white matter lesion volume, DMN connectivity differences between groups were diminished within bilateral LTC, although were significantly increased in the mPFC explained by significant regional associations between white matter lesion volume and DMN connectivity only in the MCI group. When controlling for cortical thickness, DMN FC was similarly decreased across both groups. These findings suggest that white matter lesions and cortical atrophy are differentially associated with alterations in FC patterns in MCI. Associations between white matter lesions and DMN connectivity in MCI further support at least a partial but important vascular contribution to age-associated neural and cognitive impairment.

Elevated Serum Levels of Inflammation-Related Cytokines in Mild Traumatic Brain Injury Are Associated With Cognitive Performance.

Mild traumatic brain injury (mTBI) is the most common neurological insult and leads to long-lasting cognitive impairments. The immune system modulates brain functions and plays a key role in cognitive deficits, however, the relationship between TBI-induced changes in inflammation-related cytokine levels and cognitive consequences is unclear. This was investigated in the present study in two cohorts of individuals within 1 week of mTBI (n = 52, n = 43) and 54 matched healthy control subjects. Patients with mTBI were also followed up at 1 and 3 months post-injury. Measures included cognitive assessments and a 9-plex panel of serum cytokines including interleukin (IL)-1ß, IL-4, IL-6, IL-8, IL-10, IL-12, chemokine ligand 2 (CCL2), interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α). The contribution of cytokine levels to cognitive function was evaluated by multivariate linear regression analysis. The results showed that serum levels of IL-1ß, IL-6, and CCL2 were acutely elevated in mTBI patients relative to controls; CCL2 level was remained high over 3 months whereas IL-1ß and IL-6 levels were declined by 3 months post-injury. A high level of CCL2 was associated with greater severity of post-concussion symptoms (which survived in the multiple testing correction); elevated IL-1ß was associated with worse working memory in acute phase (which failed in correction); and acute high CCL2 level predicted higher information processing speed at 3 months post-injury (which failed in correction). Thus, acute serum cytokine levels are useful for evaluating post-concussion symptoms and predicting cognitive outcome in participants with mTBI.

Sex differences in cerebral perfusion changes after mild traumatic brain injury: Longitudinal investigation and correlation with outcome.

Cerebral blood flow (CBF) is known to have marked developmental sex differences. We investigated whether gender differences exert modulatory effect on mild traumatic brain injury (mTBI) from both neuropsychological testing and brain CBF changes using a longitudinal design from acute stage to subacute 1 month post-injury. Our results supported that cognitive information processing speed (IPS), as one of core cognitive impairments following mTBI, were at least partially independent from other self-reported syndromes, such as post concussive symptom and posttraumatic stress disorder, and that it can be selectively impaired in specific male mTBI individuals. The gender difference of this cognitive domain in healthy control attenuated following mTBI and only male patients showed impaired language fluency accompanying with increased CBF changes compared with male controls. The increased CBF in the posterior parietal cortex (PPC) can predict much worse cognitive IPS performance in male patients. In contrast, female patients with mTBI displayed no impairments on any neuropsychological performance, and female sex may be a protective factor against neuropsychological impairments. Moreover, the significant interaction effect of time and gender exhibited in the left inferior frontal cortex (Broca's area). Simple effect test suggested gender differences in this area was mainly derived from the patients group at later subacute but not acute phase, for the reduced CBF at subacute mainly in the male patients. Thus, the current findings suggest that regional CBF may provide an objective biomarker for tracking gender modulatory effect on mTBI and its potentially pathological recovery process.

Disruption of periaqueductal grey-default mode network functional connectivity predicts persistent post-traumatic headache in mild traumatic brain injury.

OBJECTIVE: Post-traumatic headache (PTH) is one of the most frequent and persistent physical symptoms following mild traumatic brain injury (mTBI) and develop in more than 50% of this population. This study aimed to investigate the periaqueductal grey (PAG)-seeded functional connectivity (FC) in patients with mTBI with acute post-traumatic headache (APTH) and further examine whether the FC can be used as a neural biomarker to identify patients developing chronic pain 3 months postinjury. METHODS: 70 patients with mTBI underwent neuropsychological measurements and MRI scans within 7 days postinjury and 56 (80%) of patients were followed up at 3 months. 46 healthy controls completed the same protocol on recruitment to the study. PAG-seeded resting-state FC analysis was measured in 54 patients with mTBI with APTH, in comparison with 46 healthy volunteers. RESULTS: The mTBI+APTH group presented significantly reduced PAG-seeded FC within the default mode network (DMN), compared with healthy volunteers group. The connectivity strength can also predict patients' complaints on the impact of headache on their lives. Crucially, the initial FC strength between the PAG-right precuneus as well as the PAG-right inferior parietal lobule became the important predictor to identify patients with mTBI developing persistent PTH 3 months postinjury. CONCLUSIONS: Patients with mTBI+APTH exhibited significant PAG-related FC differences mainly within the DMN. These regions extended beyond traditional pain processing areas and may reflect the diminished top-down attention regulation of pain perception through antinociceptive descending modulation network. The disrupted PAG-DMN FC may be used as an early imaging biomarker to identify patients at risk of developing persistent PTH.