Functional connectome hierarchy of thalamus impacts fatigue in acute stroke patients.

This study aimed to explore the topographic features of thalamic subregions, functional connectomes and hierarchical organizations between thalamus and cortex in poststroke fatigue patients. We consecutively recruited 121 acute ischemic stroke patients (mean age: 59 years) and 46 healthy controls matched for age, sex, and educational level. The mean age was 59 years (range 19-80) and 38% of acute stroke patients were females. Resting-state functional and structural magnetic resonance imaging were conducted on all participants. The fatigue symptoms were measured using the Fatigue Severity Scale. The thalamic functional subdivisions corresponding to the canonical functional network were defined using the winner-take-all parcellation method. Thalamic functional gradients were derived using the diffusion embedding analysis. The results suggested abnormal functional connectivity of thalamic subregions primarily located in the temporal lobe, posterior cingulate gyrus, parietal lobe, and precuneus. The thalamus showed a gradual increase from the medial to the lateral in all groups, but the right thalamus shifted more laterally in poststroke fatigue patients than in non- poststroke fatigue patients. Poststroke fatigue patients also had higher gradient scores in the somatomotor network and the right medial prefrontal and premotor thalamic regions, but lower values in the right lateral prefrontal thalamus. The findings suggested that poststroke fatigue patients had altered functional connectivity and thalamocortical hierarchical organizations, providing new insights into the neural mechanisms of the thalamus.

Predictors and prognosis of early neurological outcomes on patients with Vertebrobasilar artery occlusion undergoing endovascular treatment.

BACKGROUND: This research explored the factors influencing early neurological outcomes (ENO) in patients who had vertebrobasilar artery occlusion (VBAO) and received endovascular treatment (EVT), as well as examining the causal influence of ENO on the prognosis of VBAO patients. METHODS: A retrospective review was carried out on patients from 65 Chinese stroke centers, all within 24 hours of the estimated occlusion time. ENO includes early neurological improvement (ENI) and early neurological deterioration (END), defined as a decrease or an increase of at least 4 points in NIHSS score between baseline and 24 hours after EVT. Death within 24 hours after EVT also consider as END. END was further divided into explainable END and unexplainable END (unEND). Independent predictors of ENO and the association between ENO and outcomes in patients with VBAO were determined using center-adjusted analyses. The study developed a multivariate logistic regression model to examine the comparative risk of unEND versus explainable END on the clinical outcomes in VBAO patients. RESULTS: A total of 2257 patients were included. Glasgow Coma Scale (GCS) (OR 1.16, 95% CI 1.03-1.30) and successful reperfusion (OR 1.15, 95% CI 1.02-1.30) were associated with ENI. Baseline NIHSS (OR 0.60, 95% CI 0.53-0.68), successful reperfusion (OR 0.79, 95% CI 0.71-0.89) and puncture to reperfusion time (OR 1.17, 95% CI 1.03-1.33) were associated with END. When examining three-month prognostic indexes, both END and ENI were found to be linked to the three-month outcomes, but in opposite directions. A subgroup analysis of END suggested that unexplained END typically demonstrated a more favorable prognosis compared to explained END, although the prognosis remained generally unfavorable. CONCLUSIONS: ENO, whether they manifested as early improvement or deterioration, were linked to the prognosis of VBAO patients undergoing EVT. The outcomes after unEND were more favorable than those following explained END.

"Catastrophic" set size limits on infants' capacity to represent objects: A systematic review and Bayesian meta-analysis.

Decades of research has revealed that humans can concurrently represent small quantities of three-dimensional objects as those objects move through space or into occlusion. For infants (but not older children or adults), this ability apparently comes with a significant limitation: when the number of occluded objects exceeds three, infants experience what has been characterized as a "catastrophic" set size limit, failing to represent even the approximate quantity of the hidden array. Infants' apparent catastrophic representational failures suggest a significant information processing limitation in the first years of life, and the evidence has been used as support for prominent theories of the development of object and numerical cognition. However, the evidence for catastrophic failure consists of individual small-n experiments that use null hypothesis significance testing to obtain null results (i.e., p > 0.05). Whether catastrophic representational failures are robust or reliable across studies, methods, and labs is not known. Here we report a systematic review and Bayesian meta-analysis to examine the strength of the evidence in favor of catastrophic representational failures in infancy. Our analysis of 22 experiments across 12 reports, with a combined total of n = 367 infants aged 10-20 months, revealed strong support for the evidence for catastrophic set size limits. A complementary analysis found moderate support for infants' success when representing fewer than four objects. We discuss the implications of our findings for theories of object and numerical cognitive development. RESEARCH HIGHLIGHTS: Previous work has suggested that infants are unable to concurrently represent four or more objects-a "catastrophic" set size limit. We reviewed this work and conducted a Bayesian meta-analysis to examine the robustness of this limit across individual small-n experiments. We found strong support for the evidence for catastrophic set size limits, and moderate support for infants' success when representing fewer than four objects.

Primary pulmonary myxoid sarcoma in the interlobar fissure of the left lung lobe: a case report.

BACKGROUND: Primary pulmonary myxoid sarcoma (PPMS) is a rare, low-grade malignant tumor, constituting approximately 0.2% of all lung tumors. Despite its rarity, PPMS possesses distinctive histological features and molecular alterations, notably the presence of EWSR1-CREB1 gene fusion. However, its precise tissue origin remains elusive, posing challenges in clinical diagnosis. CASE DEMONSTRATION: A 20-year-old male patient underwent a routine physical examination 6 months prior, revealing a pulmonary mass. Following surgical excision, microscopic evaluation unveiled predominantly short spindle-shaped tumor cells organized in a fascicular, beam-like, or reticular pattern. The stromal matrix exhibited abundant mucin, accompanied by lymphocytic and plasma cell infiltration, with Russell bodies evident in focal areas. Immunophenotypic profiling revealed positive expression of vimentin and epithelial membrane antigen in tumor cells, whereas smooth muscle actin and S-100, among others, were negative. Ki-67 proliferation index was approximately 5%. Subsequent second-generation sequencing identified the characteristic EWSR1-CREB1 gene fusion. The definitive pathological diagnosis established PPMS. The patient underwent no adjuvant chemotherapy or radiotherapy and remained recurrence-free during a 30-month follow-up period. CONCLUSIONS: We report a rare case of PPMS located within the left lung lobe interlobar fissure, featuring Russell body formation within the tumor stroma, a novel finding in PPMS. Furthermore, the histomorphological characteristics of this case highlight the diagnostic challenge it poses, as it may mimic inflammatory myofibroblastic tumor, extraskeletal myxoid chondrosarcoma, or hemangiopericytoma-like fibrous histiocytoma. Therefore, accurate diagnosis necessitates an integrated approach involving morphological, immunohistochemical, and molecular analyses.

Assess different fermentation characteristics of 54 lager yeasts based on group classification.

Saccharomyces pastorianus, hybrids of Saccharomyces cerevisiae and Saccharomyces eubayanus, were generally regarded as authentic lager beer yeasts. In recent years, with more new findings of other Saccharomyces genus hybrids, yeasts used in lager beer brewing have been proved much more complicated than previous cognition. In this study, we analyzed the different fermentation characteristics of 54 yeast strains used for lager brewing in normal and very high gravity brewing based on group classification. The difference between Group Ⅰ and Group Ⅱ lager yeasts were more striking in very high gravity brewing. However, during our research progress, we realized that some yeasts used in this study were actually hybrids of S. cerevisiae and Saccharomyces kudriavzevii. Features of these hybrids could be beneficial to very high gravity brewing. We further discussed about the mechanism behind their outstanding characteristics and the reason why group classification methods of lager beer yeasts had limitations. Hybridization in yeasts is constantly getting richer. Lager yeasts could have more possibilities based on better understandings of their genetic background and roles of other Saccharomyces genus hybrids. Their heterosis shed light on innovation in brewing and other diverse fermentation industries.

Dampening HOTAIR sensitizes the gastric cancer cells to oxaliplatin through miR-195-5p and ABCG2 pathway.

Long non-coding RNAs (lncRNA) have an extensive role in the progression and chemoresistance of gastric cancer (GC). Deeply study the regulatory role of lncRNAs could provide potential therapeutic targets. The aim of this study is to explore the regulatory role of HOTAIR in the progression and oxaliplatin resistance of GC. The expression of HOTAIR in GC and cell lines were detected by using qRT-PCR. Cell proliferation and apoptosis were analysed by CCK-8, EdU incorporation and flow cytometry. Luciferase reporter assay was used to identify the interaction between HOTAIR and ABCG2 (ATP-binding cassette (ABC) superfamily G member 2, ABCG2) via miR-195-5p. The regulatory functions were verified by using molecular biology experiments. HOTAIR was significantly overexpressed in GC and associated with poor prognosis. Knock-down of HOTAIR inhibited the GC cells proliferation and oxaliplatin resistance, while overexpression of HOTAIR showed opposite functions. Further studies found that HOTAIR acted as a competing endogenous RNA (ceRNA) to absorb miR-195-5p and elevated the expression of ABCG2, which leads to resistance of GC cells to oxaliplatin. Taken together, our findings demonstrated that HOTAIR regulates ABCG2 induced resistance of GC to oxaliplatin through miR-195-5p signalling and illustrate the great potential of developing new therapeutic targets for GC patients.

Revealing the Succession of Spatial Heterogeneity of the Microbial Community during Broad Bean Paste Fermentation.

This study aimed to elaborate the assembly processes and metabolic regulation of the microbial community under the conditions of environmental factors and artificial intervention using broad bean paste (BBP) fermentation as a tractable research object. Spatial heterogenicity of amino acid nitrogen, titratable acidity, and volatile metabolites were observed between upper and lower layers after fermentation for 2 weeks. Amino nitrogen contents in the upper fermented mash reached 0.86, 0.93, and 1.06 g/100 g at 2, 4, and 6 weeks, respectively, which were significantly higher than those of mash located at the lower layer (0.61, 0.79, and 0.78 g/100 g). Moreover, higher concentrations of titratable acidity were accumulated in upper layers (2.05, 2.25 and 2.56 g/100g) than those in lower layers, and the differentiation of volatile metabolites was the greatest (R = 0.543) at 36 days, after which the BBP flavor profiles converged with the fermentation progress. The successive heterogenicity of the microbial community in the mid-late stage was also found during fermentation, and Zygosaccharomyces, Staphylococcus, and Bacillus had heterogeneous characteristics driven by sunlight, water activity, and microbial interactions. This study provided new insights into the mechanisms underlying the succession and assembly of the microbial community of BBP fermentation, which also laid new clues for researches of the microbial communities in complex ecosystems. IMPORTANCE Gaining insights into the community assembly processes is essential and valuable for the elaboration of underlying ecological patterns. However, current studies about microbial community succession in multispecies fermented food usually treat the research object as a whole, are focused exclusively on temporal dimensions, and have ignored the changes of community structure in spatial dimensions. Therefore, dissecting the community assembly process from the view of spatiotemporal dimensions will be a more comprehensive and detailed perspective. Here, we found the heterogenicity of the BBP microbial community under the traditional production technology from spatial and temporal scales, systematically analyzed the relationship between the spatiotemporal succession of community and the difference of BBP quality, and elucidated the roles of environmental factors and microbial interactions to drive the heterogeneous succession of the microbial community. Our findings provide a new insight into understanding the association between microbial community assembly and the quality of BBP.

Non-small cell lung cancer with bone metastasis and pneumocystis pneumonia in a pregnant woman: a case report and literature review.

BACKGROUND: Cancer case during pregnancy is rare, but it is the second leading cause of maternal mortality. CASE PRESENTATION: A-32-year old pregnant woman with a gestational age of 37 weeks was admitted to the hospital due to repeated coughing for 5 months. She received Veno-Venous Extracorporeal Membrane Oxygenation (V-V ECMO) treatment for severe hypoxemia after delivery. She was diagnosed with non-small cell lung cancer (NSCLC) with bone metastasis and pneumocystis pneumonia (PCP). She subsequently received anti-tumor therapy and anti-infective therapy. After treatment, her condition improved and she was weaned from ECMO. Two weeks after weaning ECMO, her condition worsened again. Her family chose palliative treatment, and she ultimately died. CONCLUSIONS: NSCLC is rare during pregnancy. At present, there is still a lack of standardized methods to manage these cases. For theses cases, the clinician should be wary of opportunistic infections, such as pneumocystis jirovecii (P. jirovecii) and Elizabethkingia spp. Specialized medical teams with abundant experience and multidisciplinary discussions from the perspectives of the patient's clinical characteristics as well as preferences are crucial for developing individualized and the best approach.

Inflammatory myofibroblastic tumour of the common bile duct: a case report and literature review.

INTRODUCTION: Inflammatory myofibroblastic tumour (IMT) of the common bile duct (CBD) is an extremely rare low-grade malignancy with various biological behaviours and a lack of specific clinical and histopathological features. Preoperative and intraoperative diagnosis are challenging, and a diagnostic delay may increase surgical complexity. CASE PRESENTATION: We present the case of a 34-year-old male with no relevant medical history who presented with jaundice of 20 days of evolution. Histology and immunohistochemistry confirmed the diagnosis of an IMT with anaplastic lymphoma kinase (ALK)-1 expression. In addition, a review of the relevant literature revealed 13 published reports of biliary IMTs. The clinical history and histopathological features in these 13 cases were compared with those in our case to provide a comprehensive overview of the clinical manifestations and histopathological features of the disease. CONCLUSION: IMT of the CBD is an extremely rare low-grade malignancy that mainly occurs in middle-aged female patients. The main clinical manifestation is monosymptomatic jaundice. The reported tumours originated in the middle and lower segments of the CBD, with an average size of approximately 3.5 cm × 3.0 cm and tumour cells expressing smooth muscle actin (SMA), vimentin and ALK. Abnormal ALK expression and ALK gene rearrangement represent potential histopathological and differential diagnoses. A clear diagnosis by preoperative biopsy and intraoperative frozen section examination is critical and can significantly reduce surgical trauma. The prognosis is good, and very few patients experience recurrence or distant metastasis.

What aspects of counting help infants attend to numerosity?

Recent work shows that 18-month old infants understand that counting is numerically relevant-infants who see objects counted are more likely to represent the approximate number of objects in the array than infants who see the objects labeled but not counted. Which aspects of counting signal infants to attend to numerosity in this way? Here we asked whether infants rely on familiarity with the count words in their native language, or on procedures instantiated by the counting routine, independent of specific tokens. In three experiments (N = 48), we found that 18-month old infants from English-speaking households successfully distinguished four hidden objects from two when the objects were counted correctly, regardless of their familiarity with the count words (i.e., when objects were counted in familiar English and in unfamiliar German). However, when the objects were counted using familiar English count words in ways that violated basic counting principles, infants no longer represented the arrays, failing to distinguish four hidden objects from two. Together with previous findings, these results suggest that children may link the procedure of counting with numerosity years before they learn the meanings of the count words.

Se-H-free As2Se3 fiber and its spectral applications in the mid-infrared.

The complete removal of the impurities like Se-H in Se-based chalcogenide glasses has been challenging in the development of highly transparent chalcogenide glass fiber. In this paper, several purification methods, including dynamic distillation, static distillation, and combined distillation method, were adopted with an aim of purifying arsenic selenide glass with ultra-low content of the impurities. The experimental results demonstrated that the Se-H can be completely eliminated in the arsenic selenide glass host and fiber without the introduction of any chloride. We further explored the applications of such low loss and Se-H-free chalcogenide glass fiber in the mid-infrared. It was found that, using such a Se-H free fiber, a flattened supercontinuum spectrum above the -30 dB level from 1.2 to 13 µm was generated from the Se-H free fiber with a 5.5 µm laser pumping. The sensitivity was found to be improved 5.1 times for CO2 gas in the 3 to 6 µm wavelength range.

Primary central nervous system CD20-negative diffuse large B-cell lymphoma: a case report.

BACKGROUND: CD20-negative diffuse large B-cell lymphoma is a very rare and heterogeneous invasive cancer characterized by chemical resistance and poor prognosis. Primary CD20-negative diffuse large B-cell lymphoma of the central nervous system is even rarer, presenting great challenges in pathological diagnosis and clinical treatment. CASE PRESENTATION: We report a case of primary CD20-negative diffuse large B-cell lymphoma of the CNS in a 54-year-old woman admitted to the hospital with a headache lasting more than 10 days. CT and MRI scans showed right temporal lobe lymphoma. Microscopically, large infiltrating lymphoid cells that induced brain tissue damage were observed. Immunohistochemistry showed that the tumor cells were CD79a+, PAX-5+, MUM1+, and CD20-. The patient was diagnosed with lymphoma and transferred to an oncology hospital for chemotherapy. However, because the disease progressed rapidly, the patient died only after two rounds of chemotherapy. CONCLUSIONS: To the best of our knowledge, this is one of the first reported cases of unclassifiable CD20-negative diffuse large B-cell lymphoma located in the CNS. This case report aims to deepen the understanding of clinicopathological features of this type of lymphoma and expand the scope of this disease.

Isolated splenic mucormycosis secondary to diabetic ketoacidosis: a case report.

BACKGROUND: Mucormycosis is a rare but serious opportunistic fungal infection that occurs in immunocompromised individuals, especially those with diabetic ketoacidosis. Presently, early diagnosis of the disease remains a challenge for clinicians. CASE PRESENTATION: The patient, a 68-year-old woman with type 2 diabetes mellitus, was admitted with paroxic sharp pain in the left upper abdomen. CT imaging revealed a patchy hypodense shadow of the spleen with wedge-shaped changes. The patient was not considered early for fungal infection. The diagnosis of spleen mucormycosis was not confirmed until pathological biopsy after splenectomy. After surgery, blood glucose level was controlled, acidosis was corrected, and antifungal therapy was effective. CONCLUSIONS: We report here, for the first time ever, a case of isolated splenic mucormycosis secondary to diabetic ketoacidosis that was diagnosed and treated with antifungal drugs and splenectomy. Following splenectomy, the presence of splenic mucormycosis was confirmed when characteristic mycelia were observed in a tissue biopsy. As the location of any fungal infection is extremely relevant for treatment options and prognoses, early diagnosis and clinical intervention can greatly affect outcomes and prognoses for patients.

A rare case of extraintestinal amebiasis.

BACKGROUND: Amoebiasis is caused by the protozoan Entamoeba histolytica, which is a rare infectious disease in developed countries. If the trophozoites enter the blood, it can spread through the body, such as brain, and lungs. Cases of simultaneous infection of multiple organs are extremely rare. CASE PRESENTATION: Here we report a case of simultaneous infection of amoeba in pulmonary pleura, urinary system and central nervous system. Although the patient received anti amoeba treatment, the prognosis of the patient was poor. CONCLUSIONS: In this patient, multiple extraintestinal amebic infections in the absence of clinically confirmed intestinal amebiasis or amebic liver abscess are rare and pose diagnostic challenges. The disseminated amebiasis has significantly increased the mortality. Early diagnosis and appropriate treatment may reduce the mortality of disseminated amebiasis.

Transcriptomic and metabolomic analysis reveals genes related to stress tolerance in high gravity brewing.

The fermentation performance of yeast is the key of beer production. High gravity brewing is a commonly used technique in industrial lager beer production and it is environmentally friendly. Therefore, there has been extensive effort toward improving high gravity brewing. In this study, through transcriptomic and metabolomic analysis of two homologous lager yeasts, genes that relate to stress tolerance in high gravity brewing were screened. The results showed EMP pathway and multiple amino acid metabolism pathway were the most enriched pathways, and pyruvate might be the core metabolite. Overexpression and knockdown strains were constructed to verify the genes' functions. The overexpression of MAN2, PCL1 and PFK26 genes were beneficial to fermentation without significantly changes in flavor profiles. The relative intracellular ATP levels can help us understand the change of metabolic flux such as enhancement of sugar consumption. This work is helpful to reveal the stress tolerance mechanism of high gravity brewing and breed yeast strains with improved performance.

[Effects of Porphyra yezoensis extract on hepatic inflammatory factors and oxidative stress in type 1 diabetic mice].

OBJECTIVE: To study the effect of Porphyra yezoensis extract on liver inflammation and oxidative stress in type 1 diabetics mice. METHODS: A total of ninety-one C57 BL/6 J male mice were adaptively fed for two weeks, and twelve C57 BL/6 J male mice were randomly reserved to be included in the blank control group. The rest of the mice were fasted overnight for twelve hours(except water), and they were given 170.00 mg/kg streptozotocin by intraperitoneal injection. Fasting blood glucose in type 1 diabetics mice were greater than or equal to 16.7 mmol/L after seven days, and polydipsia, polyphagia, polyuria and weight loss appeared, which were judged to be the successful model of type 1 diabetes. Forty-eight successfully modeled mice were divided into the model control group, the low dose of Porphyra yezoensis extract group, the medium dose of Porphyra yezoensis extract and high dose of Porphyra yezoensis extract group according to the fasting blood glucose and body weight. The mice in the blank control group and the model group were given the same amount of normal saline. The low-dose, medium-dose, and high-dose intervention groups were separately given the corresponding dose of Porphyra yezoensis extract by intragastric administration for six weeks. The body weight of type 1 diabetic mice, changes in body length, fasting blood glucose, insulin, liver inflammatory factors and oxidative stress indicators and pathological sections of liver and pancreas after the intervention of Porphyra yezoensis extract were observed. The glucose oxidase method was used to determine the fasting blood glucose level of type 1 diabetic mice. The serum insulin content, liver inflammatory factor levels and oxidative stress indicators were detected by the enzyme-linked immunosorbent assay(ELISA). The hematoxylin-eosin staining method was used to observe histopathology of liver and pancreas paraffin sections. RESULTS: The weight of the model control group was significantly lower than that of the blank control group(P<0.05), and the fasting blood glucose value was significantly higher than that of the blank control group(P<0.05). There was no statistical difference. In terms of inflammatory factors, compared with the model control group, low-dose Porphyra yezoensis extract can increase serum insulin levels and reduce liver tumor necrosis factor-α(TNF-α) levels(P<0.05) in T1DM mice, and medium-dose Porphyra yezoensis extract can reduce liver TNF-α level(P<0.05), high-dose Porphyra yezoensis extract can reduce the level of interleukin-1ß(IL-1ß)(P<0.05). The histopathological conditions of pancreas in different intervention groups were improved compared with the model control group, and the number of ß cells increased compared with the model group. In terms of oxidative stress, compared with the model control group, low-dose Porphyra yezoensis extract can significantly reduce the levels of liver alanine aminotransferase(ALT) and malondialdehyde(MDA)(P<0.05), and high-dose Porphyra yezoensis extract can significantly increase the levels of glutathione peroxidase(GSH-Px) and catalase(CAT)(P<0.05). CONCLUSION: The protective effect of Porphyra yezoensis extract on liver oxidative damage in T1DM mice may be achieved by regulating the activity of CAT and GSH-Px and reducing the content of MDA. In addition, Porphyra yezoensis extract can reduce liver TNF-α and IL-1ß levels to improve liver inflammation.

Children With More Uncertainty in Their Intuitive Theories Seek Domain-Relevant Information.

How do changes in learners' knowledge influence information seeking? We showed preschoolers (N = 100) uncertain outcomes for events and let them choose which event to resolve. We found that children whose intuitive theories were at immature stages were more likely to seek information to resolve uncertainty about an outcome in the related domains, but children with more mature knowledge were not. This result was replicated in a second experiment but with the nuance that children at intermediate stages of belief development-when the causal outcome would be most ambiguous-were the most motivated to resolve the uncertainty. This effect was not driven by general uncertainty at the framework level but, rather, by the impact that framework knowledge has in accessing uncertainty at the model level. These results are the first to show the relationship between a learning preference and the developmental stage of a child's intuitive theory.

Genome comparison of three lager yeasts reveals key genes affecting yeast flocculation during beer fermentation.

Yeast flocculation plays an essential role in industrial application. Appropriate flocculation of yeast cells at the end of fermentation benefits the cell separation in production, which is an important characteristic of lager yeast for beer production. Due to the complex fermentation environment and diverse genetic background of yeast strains, it is difficult to explain the flocculation mechanism and find key genes that affect yeast flocculation during beer brewing. By analyzing the genomic mutation of two natural mutant yeasts with stronger flocculation ability compared to the parental strain, it was found that the mutated genes common in both mutants were enriched in protein processing in endoplasmic reticulum, membrane lipid metabolism and other pathways or biological processes involved in stress responses. Further functional verification of genes revealed that regulation of RIM101 and VPS36 played a role in lager yeast flocculation under the brewing condition. This work provided new clues for improving yeast flocculation in beer brewing.

Stressful life events can predict post-stroke fatigue in patients with ischemic stroke.

OBJECTIVE: To investigate whether stressful life events (SLEs) can predict post-stroke fatigue (PSF) in patients with acute ischemic stroke (AIS). METHODS: This prospective cohort study included data from patients with AIS who were followed up to 2-year interview. PSF was assessed at admission and at 6 (n = 916), 12 (n = 880), and 24 (n = 857) months with the fatigue severity scale (FSS). SLEs were measured with the Social Readjustment Rating Scale questionnaire at 6, 12 and 24 months' interview. RESULTS: A significant dose-response association was found between SLEs and FSS score across all examined time-points: compared with those did not experience SLEs, FSS score was higher for those experiencing SLEs ≥3 at 6 months (ß 0.53, 95% CI 0.28-0.78), 12 months (ß 0.54, 95% CI 0.30-0.78) and 24 months (ß 0.48, 95% CI 0.29-0.68). Longitudinal analyses indicated a significantly positive relationship between the number of SLEs and FSS score (SLEs: ≥3 vs. 0, ß 0.14, 95% CI 0.09-0.19). Moreover, a distinct interaction of follow-up time and SLE numbers on FSS score was observed (p < 0.05), which means elevated exposure to SLEs during follow-up was associated with a lower rate of fatigue decline. A similar association was found in SLE load analysis. CONCLUSION: Patients with severe fatigue were more likely to report increased number of SLEs in the previous 6 months, which could suggest that a non-specific stressful event leads to an extra burden to an already vulnerable psychological system.

Emergence of the Link Between the Approximate Number System and Symbolic Math Ability.

Experimentally manipulating Approximate Number System (ANS) precision has been found to influence children's subsequent symbolic math performance. Here in three experiments (N = 160; 81 girls; 3-5 year old) we replicated this effect and examined its duration and developmental trajectory. We found that modulation of 5-year-olds' ANS precision continued to affect their symbolic math performance after a 30-min delay. Furthermore, our cross-sectional investigation revealed that children 4.5 years and older experienced a significant transfer effect of ANS manipulation on math performance, whereas younger children showed no such transfer, despite experiencing significant changes in ANS precision. These findings support the existence of a causal link between nonverbal numerical approximation and symbolic math performance that first emerges during the preschool years.