The dynamic causality brain network reflects whether the working memory is solidified.

Working memory, which is foundational to higher cognitive function, is the "sketchpad of volitional control." Successful working memory is the inevitable outcome of the individual's active control and manipulation of thoughts and turning them into internal goals during which the causal brain processes information in real time. However, little is known about the dynamic causality among distributed brain regions behind thought control that underpins successful working memory. In our present study, given that correct responses and incorrect ones did not differ in either contralateral delay activity or alpha suppression, further rooting on the high-temporal-resolution EEG time-varying directed network analysis, we revealed that successful working memory depended on both much stronger top-down connections from the frontal to the temporal lobe and bottom-up linkages from the occipital to the temporal lobe, during the early maintenance period, as well as top-down flows from the frontal lobe to the central areas as the delay behavior approached. Additionally, the correlation between behavioral performance and casual interactions increased over time, especially as memory-guided delayed behavior approached. Notably, when using the network metrics as features, time-resolved multiple linear regression of overall behavioral accuracy was exactly achieved as delayed behavior approached. These results indicate that accurate memory depends on dynamic switching of causal network connections and shifting to more task-related patterns during which the appropriate intervention may help enhance memory.

Genomics of clonal evolution in a rare essential thrombocythemia with coexisting Type 2 CALR and MPL S204P mutations.

Essential thrombocythemia (ET) with double driver mutations is a rare disease. ET patients with both MPL and Type 1 CALR mutations have been reported. Here, we report the first case of an ET patient with both MPL S204P and Type 2 CALR mutations and a summary of our literature review findings. In the patient whose case is reported here, the disease progressed to an accelerated phase 3.5 months after diagnosis. CALR mutation disappeared and new mutations emerged as the disease progressed, such as ASXL1, CBL, ETV6, and PTPN11 mutations. This case highlights that screening for additional mutations using NGS should be considered in patients with ET to assess the prognosis, especially as the disease progresses.

Robotic versus Laparoscopic Total Mesorectal Excision Surgery in Rectal Cancer: Analysis of Medium-Term Oncological Outcomes.

Background. Robotic systems can overcome some limitations of laparoscopic total mesorectal excision (L-TME), thus improving the quality of the surgery. So far, many studies have reported the technical feasibility and short-term oncological results of robotic total mesorectal excision (R-TME) in treating rectal cancer (RC); however, only a few evaluated the survival and long-term oncological outcomes. The following study compared the medium-term oncological data, 3-year overall survival (OS), and disease-free survival (DFS) of L-TME and R-TME in patients with rectal cancer. Methods. In this retrospective study, records of patients (patients with stage I-III rectal cancer) who underwent surgery (127 cases of L-TME and 148 cases of R-TME) at the Gansu Provincial Hospital between June 2016 and March 2018 were included in the analysis. Kaplan-Meier analysis evaluated the 3-year OS and DFS for all patients treated with curative intent. Results. The conversion rate was significantly higher, and the postoperative hospital stay was significantly longer in the L-TME group than in the R-TME group (all P<.05). Major complications were significantly lower in the robotic group (P<.05). The 3-year DFS rate (for all stages) was 74.8% for L-TME and 85.8% for R-TME (P = .021). For disease stage III, the 3-year DFS and OS were significantly higher in the R-TME group (P<.05). Conclusion. R-TME can achieve better oncological outcomes and is more beneficial for RC patients compared with L-TME, especially for those with stage III rectal cancers. Nevertheless, further randomized controlled trials and a longer follow-up period are needed to confirm these findings.

DKK1 suppresses WWP2 to enhance bortezomib resistance in multiple myeloma via regulating GLI2 ubiquitination.

Bortezomib-based chemotherapy represents the most prevalent regimens for multiple myeloma (MM), whereas acquired drug resistance remains a major obstacle. Myeloma cells often produce excessive amount of dickkopf-1 (DKK1), giving rise to myeloma bone disease. However, it remains obscure about the effects and mechanisms of DKK1 in the progression and bortezomib responsiveness of MM cells. In the current study, we found WWP2, an E3 ubiquitin-protein ligase, was downregulated in the bortezomib-resistant cells along with high expression of DKK1. Further investigation revealed that WWP2 was a direct target of Wnt/ß-catenin signaling pathway, and DKK1 suppressed the expression of WWP2 via canonical Wnt signaling. We further identified that WWP2 mediated the ubiquitination and degradation of GLI2, a main transcriptional factor of the Hedgehog (Hh) pathway. Therefore, DKK1-induced WWP2 downregulation improved GLI2 stability and activation of Hh signaling pathway, contributing to the resistance to bortezomib of MM cells. Clinical data also validated that WWP2 expression was associated with the treatment response and clinic outcomes of MM patients. WWP2 overexpression restricted MM progression and enhanced cell sensitivity to bortezomib treatment in vitro and in vivo. Taken together, our findings demonstrate that DKK1 facilitates the generation of bortezomib resistance in MM via downregulating WWP2 and activating Hh pathway. Thus, the manipulation of DKK1-WWP2-GLI2 axis might sensitize myeloma cells to proteasome inhibitors.

Better estimation of evapotranspiration and transpiration using an improved modified Priestly-Taylor model based on a new parameter of leaf senescence in a rice field.

Evapotranspiration (ET) is at the heart of the global water, energy, and carbon cycles. As ET is difficult and expensive to measure, it is crucial to develop estimation models that can be widely applied. Currently, an improved Priestley-Taylor (PT) model considers soil moisture stress, temperature constraints, and leaf senescence; however, its parameter (fs) for simulating crop senescence is based on empirical values, making it difficult to apply to different varieties and complex external conditions and thus challenging to generalize. We improved the parameters fs in the original model based on the chlorophyll decomposition that accompanies crop senescence through easily observable SPAD values (Soil-Plant Analysis Development readings) in the field. We validated the improved model by obtaining ET of different rice varieties in 2022 and 2023 using the energy balance residual method at the Free Air Concentration Enrichment Experimental (FACE) Facility located in Yangzhou City, China. The results showed that the simulation of leaf senescence using SPAD values was feasible and could be extended to different varieties. The new model using improved leaf senescence parameter for estimating ET and transpiration (T) in three plots (2022 and 2023) exhibited slightly enhanced accuracy, particularly at the later stages of crop growth. Moreover, the higher the T/ET ratio of the cropland, the more significant the improvement. This new development enhances the ability of PT models to estimate ET and T using readily available field observations and provides some suggestions for wider application in the field for other crop species.

EEG brain network variability is correlated with other pathophysiological indicators of critical patients in neurology intensive care unit.

Continuous electroencephalogram (cEEG) plays a crucial role in monitoring and postoperative evaluation of critical patients with extensive EEG abnormalities. Recently, the temporal variability of dynamic resting-state functional connectivity has emerged as a novel approach to understanding the pathophysiological mechanisms underlying diseases. However, little is known about the underlying temporal variability of functional connections in critical patients admitted to neurology intensive care unit (NICU). Furthermore, considering the emerging field of network physiology that emphasizes the integrated nature of human organisms, we hypothesize that this temporal variability in brain activity may be potentially linked to other physiological functions. Therefore, this study aimed to investigate network variability using fuzzy entropy in 24-hour dynamic resting-state networks of critical patients in NICU, with an emphasis on exploring spatial topology changes over time. Our findings revealed both atypical flexible and robust architectures in critical patients. Specifically, the former exhibited denser functional connectivity across the left frontal and left parietal lobes, while the latter showed predominantly short-range connections within anterior regions. These patterns of network variability deviating from normality may underlie the altered network integrity leading to loss of consciousness and cognitive impairment observed in these patients. Additionally, we explored changes in 24-hour network properties and found simultaneous decreases in brain efficiency, heart rate, and blood pressure between approximately 1 pm and 5 pm. Moreover, we observed a close relationship between temporal variability of resting-state network properties and other physiological indicators including heart rate as well as liver and kidney function. These findings suggest that the application of a temporal variability-based cEEG analysis method offers valuable insights into underlying pathophysiological mechanisms of critical patients in NICU, and may present novel avenues for their condition monitoring, intervention, and treatment.

A One-Step Multiplex PCR Method to Rapidly Distinguish Two Strains of Diglyphus wani (Hymenoptera: Eulophidae) Against Agromyzid Leafminers.

Hymenopteran parasitoids generally show a haplo-diploid sex determination system. Haploid males are produced from unfertilized eggs, whereas diploid females develop from fertilized eggs (arrhenotokous). In some cases, diploid females develop from unfertilized eggs (thelytokous). Diglyphus wani (Hymenoptera: Eulophidae) is a biological control agent for agromyzid leafminers and have arrhenotokous and thelytokous strains. However, the morphological characteristics of two strains of D. wani are so similar that it is difficult to accurately distinguish them based on morphology. Here, a rapid molecular identification method was developed based on the mitochondrial gene cytochrome c oxidase I (COI) and one-step multiplex PCR. Two primer combinations, PC1 (Ar-F1/Th-F1/WR2) and PC2 (Ar-F1/Th-F4/WR2), were designed and repeatedly screened to distinguish two strains simultaneously, of which two special forward primers Th-F1/Th-F4 were used for the thelytokous strain and one special forward primer Ar-F1 was used for the arrhenotokous strain. In addition, a common reverse primer, WR2, was used for both strains. The PC1 and PC2 PCR assays were effective in distinguishing the two strains at different developmental stages and field colonies. This method provides a reliable, highly sensitive, and cost-effective tool for the rapid identification of the two strains of D. wani.

Effect of flexible sigmoidoscopy-based screening on colorectal cancer incidence and mortality: an updated systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: Our objective was to estimate the effect of flexible sigmoidoscopy (FS)-based screening on colorectal cancer (CRC) incidence and mortality by conducting an updated meta-analysis of randomized controlled trials (RCTs). METHODS: PubMed, Web of Science, Embase, and Cochrane Library searched for RCTs from database inception to December 2022. The methodological quality of the RCTs was assessed using the Cochrane Collaboration Risk of Bias Tool. RevMan 5.4 was used for this meta-analysis. RESULTS: Four RCTs involving 457, 871 patients were included. This meta-analysis revealed that FS-based screening was associated with a 20% relative risk reduction in CRC incidence [RR = 0.80; 95% CI (0.75, 0.86); P < 0.00001], and a 24% reduction in CRC mortality [RR = 0.76; 95% CI (0.70, 0.82); P < 0.00001]. In addition, this meta-analysis revealed that FS-based screening reduced the incidence[RR = 0.68; 95% CI (0.60, 0.77); P < 0.00001] and mortality[RR = 0.64; 95% CI (0.49, 0.83); P = 0.0007] of distal CRC, but had no significant effect on proximal colon cancer. CONCLUSION: FS-based screening appeared to be effective in reducing distal CRC incidence and mortality in patients at average risk compared to no intervention, but had no significant effect on proximal colon cancer.

Apomixis for no bacteria-induced thelytoky in Diglyphus wani (Hymenoptera: Eulophidae).

In Hymenoptera species, the reproductive mode is usually arrhenotoky, where haploid males arise from unfertilized eggs and diploid females from fertilized eggs. In addition, a few species reproduce by thelytoky, where diploid females arise from unfertilized eggs. Diploid females can be derived through various cytological mechanisms in thelytokous Hymenoptera species. Hitherto, these mechanisms were revealed mainly in endosymbiont-induced thelytokous Hymenoptera species. In contrast, thelytokous Hymenoptera species in which a reproductive manipulator has not been verified or several common endosymbionts have been excluded were paid less attention in their cytological mechanisms, for instance, Diglyphus wani (Hymenoptera: Eulophidae). Here, we investigated the cytological mechanism of D. wani using cytological methods and genetic markers. Our observations indicated that the diploid karyotypes of two strains of D. wani consist of four pairs of relatively large metacentric chromosomes and one pair of short submetacentric chromosomes (2n = 10). The arrhenotokous strains could complete normal meiosis, whereas the thelytokous strain lacked meiosis and did not expulse any polar bodies. This reproductive type of lacking meiosis is classified as apomictic thelytoky. Moreover, a total of 636 microsatellite sequences were obtained from thelytokous D. wani, dominated by dinucleotide repeats. Genetic markers results showed all three generations of offspring from thelytokous strain maintained the same genotype as their parents. Our results revealed that D. wani is the first eulophid parasitoid wasp in Hymenoptera whose thelytoky was not induced by bacteria to form an apomictic thelytoky. These findings provide a baseline for future inner molecular genetic studies of ameiotic thelytoky.

Risk factors associated with loss to follow-up of breast cancer patients: A retrospective analysis.

BACKGROUND: Loss to follow-up (LTFU) during post-operative surveillance of breast cancer patients is detrimental. The pattern of LTFU and its risk factors in Chinese breast cancer patients remains unknown. METHOD: Eligible non-metastatic breast cancer patients who underwent surgery at our institution between 2009 and 2012 were included. The clinicopathological features, as well as the LTFU status, were retrieved from the REDCap database. LTFU was defined as the absence of patients for at least 12 months since her last contact. 5-year LTFU was defined as the LTFU status of each patients at 5 years after surgery. The incidence and potential risk factors of LTFU were analyzed. A LTFU-risk score was developed to quantify the risk of LTFU. RESULTS: A total of 1536 patients with breast cancer were included, and 411(26.8%) patients were 5-year LTFU. 198 patients were LTFU in the first year. Univariate and multivariate analysis revealed that age (younger and older), a lack of medical insurance, longer distance from residence to the hospital, pathology (DCIS/Paget's/Phyllodes), lymph node metastasis, the absence of endocrine therapy and fewer than five contact numbers were significantly and independently associated with the risk of LTFU. A LTFU-risk score was developed and was predictive of LTFU. CONCLUSIONS: A series of risk factors were significantly associated with post-operative LTFU of breast cancer patients. Patients with different risks of LTFU could possibly be identified, and surveillance plans could be individualized for different patients, so as to effectively reduce the overall LTFU rate, and optimize the allocation of medical resources.

Controllability of Networks of Multiple Coupled Neural Populations: An Analytical Method for Neuromodulation's Feasibility.

Neuromodulation plays a vital role in the prevention and treatment of neurological and psychiatric disorders. Neuromodulation's feasibility is a long-standing issue because it provides the necessity for neuromodulation to realize the desired purpose. A controllability analysis of neural dynamics is necessary to ensure neuromodulation's feasibility. Here, we present such a theoretical method by using the concept of controllability from the control theory that neuromodulation's feasibility can be studied smoothly. Firstly, networks of multiple coupled neural populations with different topologies are established to mathematically model complicated neural dynamics. Secondly, an analytical method composed of a linearization method, the Kalman controllable rank condition and a controllability index is applied to analyze the controllability of the established network models. Finally, the relationship between network dynamics or topological characteristic parameters and controllability is studied by using the analytical method. The proposed method provides a new idea for the study of neuromodulation's feasibility, and the results are expected to guide us to better modulate neurodynamics by optimizing network dynamics and network topology.

Consumption-based greenhouse gas emissions accounting with capital stock change highlights dynamics of fast-developing countries.

Traditional consumption-based greenhouse gas emissions accounting attributed the gap between consumption-based and production-based emissions to international trade. Yet few attempts have analyzed the temporal deviation between current emissions and future consumption, which can be explained through changes in capital stock. Here we develop a dynamic model to incorporate capital stock change in consumption-based accounting. The new model is applied using global data for 1995-2009. Our results show that global emissions embodied in consumption determined by the new model are smaller than those obtained from the traditional model. The emissions embodied in global capital stock increased steadily during the period. However, capital plays very different roles in shaping consumption-based emissions for economies with different development characteristics. As a result, the dynamic model yields similar consumption-based emissions estimation for many developed countries comparing with the traditional model, but it highlights the dynamics of fast-developing countries.

Effect of flow and stretch on the [Ca2+]i response of principal and intercalated cells in cortical collecting duct.

An acute increase in tubular fluid flow rate in the microperfused cortical collecting duct (CCD), associated with a approximately 20% increase in tubular diameter, leads to an increase in intracellular Ca2+ concentration ([Ca2+]i)in both principal and intercalated cells (Woda CB, Leite M Jr, Rohatgi R, and Satlin LM. Am J Physiol Renal Physiol 283: F437-F446, 2002). The apical cilium present in principal but not intercalated cells has been proposed to be a flow sensor. To determine whether flow across the cilium and/or epithelial stretch mediates the [Ca2+]i response, CCDs from New Zealand White rabbits were microperfused in vitro, split-open (to isolate the effect of flow across cilia), or occluded (to examine the effect of stretch and duration/magnitude of the flow impulse), and [Ca2+]i was measured using fura 2. In perfused and occluded CCDs, a rapid (<1 s) but not slow (>3 min) increase in luminal flow rate and/or circumferential stretch led to an approximately threefold increase in [Ca2+]i in both principal and intercalated cells within approximately 10 s. This response was mediated by external Ca2+ entry and inositol 1,4,5-trisphosphate-mediated release of cell Ca2+ stores. In split-open CCDs, an increase in superfusate flow led to an approximately twofold increase in [Ca2+]i in both cell types within approximately 30 s. These experimental findings are interpreted using mathematical models to predict the fluid stress on the apical membranes of the CCD and the forces and torques on and deformation of the cilia. We conclude that rapid increases in luminal flow rate and circumferential stretch, leading to shear or hydrodynamic impulses at the cilium or apical membrane, lead to increases in [Ca2+]i in both principal and intercalated cells.