Addressing causal relationship between drinking behavior and metabolic syndrome: one-sample Mendelian randomization analysis.

AIMS: Alcohol drinking is associated with central obesity, hypertension, and hyperlipidemia, which further causes metabolic syndrome (MetS). However, prior epidemiological studies on such associations lack experimental evidence for a causal relationship. This study aims to explore the causal relationship between drinking behavior and MetS in Taiwan population by using Mendelian randomization (MR) analysis. METHODS: A cross-sectional study was conducted using the Taiwan Biobank database, which comprised 50 640 Han Chinese who were 30-70 years old without cancer from 2008 to 2020. In MR analysis, we constructed weighted and unweighted genetic risk scores by calculating SNP alleles significantly associated with alcohol drinking. We calculated odds ratios and 95% confidence interval (CI) by using a two-stage regression model. RESULTS: A total of 50 640 participants were included with a mean age of 49.5 years (SD: 1.67 years), 36.6% were men. The adjusted odds ratio (aOR) of MetS per 5% increase in the likelihood of genetic predisposition to drink based on weighted genetic risk score with adjustment was 1.11 (95% CI: 1.10, 1.12, P < .001). Analysis was also conducted by grouping the likelihood of genetic predisposition to drink based on quartiles with multivariate adjustment. Using Q1 as the reference group, the aORs of MetS for Q2, Q3, and Q4 were 1.19 (1.12, 1.27, p < .001), 1.31 (1.23, 1.40, p < .001), and 1.87 (1.75, 2.00, p < .001), respectively, for the weighted genetic risk score. CONCLUSIONS: This study shows a modest relationship between drinking behavior and MetS by using MR analysis.

Mitochondrial DNA haplogroup D and brain microstructure regulate cognitive function among community-dwelling older adults.

INTRODUCTION: Maintaining physical and cognitive function among older adults is important. These functional states are affected by mitochondria through various mechanisms, such as cellular energy production and oxidative stress control. Owing to its involvement in the relations among the brain, cognition, and physical function, mitochondrial function may be affected by mitochondrial DNA (mtDNA) haplogroups. This study explored the effect of mtDNA haplogroups and brain microstructure on physical and cognitive functions among community-dwelling older adults. METHODS: This study was a community-based cross-sectional research. A total of 128 subjects aged 65 years and older without dementia completed several assessments, including mtDNA sequencing, physical and cognitive function tests, and magnetic resonance imaging (MRI) scans. Cognitive function and impairment were assessed by the MMSE and AD8 questionnaires. mtDNA haplogroups were classified by HaploGrep 2 software, and white matter microstructural integrity was scanned by 3T MRI. RESULTS: The mean age of the subjects was 77.3 years. After the adjustment for covariates, the mtDNA haplogroup D carriers showed significantly lower mini-mental state examination (MMSE) scores than other carriers (p = 0.047). Further considering the brain microstructure, the mtDNA haplogroup D (p = 0.002) and white matter volumes in the left precuneus corrected for total intracranial volumes (p = 0.014) were found to be independently influencing factors of the MMSE scores. CONCLUSIONS: The mtDNA haplogroup D and white matter microstructure regulated the cognitive function among community-dwelling older adults. The findings provide new insights into the research gap. Scientists must further venture into this field.

Phytochrome B inhibits the activity of phytochrome-interacting factor 7 involving phase separation.

Shade-intolerant plants sense changes in the light environment and trigger shade-avoidance syndrome in the presence of neighboring vegetation. Phytochrome-interacting factor 7 (PIF7) is an essential regulator that integrates shade signals into plant transcriptional networks. While the regulation of PIF7 under shade conditions has been well studied, the mechanism that represses PIF7 activity under white light remains ambiguous. Here, we report that PIF7 forms nuclear puncta containing phase-separated liquid-like condensates. Phytochrome B (phyB) then binds to dephosphorylated PIF7 and promotes its condensed phase of PIF7 under white light. The phyB-PIF7 condensate subsequently inhibits the DNA-binding activity of PIF7. However, shade inactivation of phyB causes the dissociation of phyB-PIF7 condensates and allows unbound PIF7 to promote the transcription of shade-induced genes. This reversible transcriptional condensation via phase separation provides sessile organisms with the flexibility of gene control to adapt to their surrounding environment.

Characterization and clinical implications of different malignant transformation patterns in diffuse low-grade gliomas.

Malignant transformation (MT) of low-grade gliomas (LGGs) to a higher-grade variant seems inevitable, yet it remains unclear which LGG patients will progress to grade 3 or even directly to grade 4 after receiving a long course of treatment. To elucidate this, we conducted a retrospective cohort study based on 229 adults with recurrent LGG. Our study aimed to disclose the characteristics of different MT patterns and to build predictive models for patients with LGG. Patients were allocated into group 2-2 (n = 81, 35.4%), group 2-3 (n = 91, 39.7%), and group 2-4 (n = 57, 24.9%), based on their MT patterns. Patients who underwent MT showed lower Karnofsky performance scale (KPS) scores, larger tumor sizes, smaller extents of resection (EOR), higher Ki-67 indices, lower rates of 1p/19q codeletion, but higher rates of subventricular involvement, radiotherapy, chemotherapy, astrocytoma, and post-progression enhancement (PPE) compared with those in group 2-2 (p < 0.01). On multivariate logistic regression, 1p/19q codeletion, Ki-67 index, radiotherapy, EOR, and KPS score were independently associated with MT (p < 0.05). Survival analyses demonstrated that patients in group 2-2 had the longest survival, followed by group 2-3 and then group 2-4 (p < 0.0001). Based on these independent parameters, we constructed a nomogram model that exhibited superior potential (sensitivity: 0.864, specificity: 0.814, and accuracy: 0.843) compared with PPE in early prediction of MT. Combining the factors of 1p/19q codeletion, Ki-67 index, radiotherapy, EOR, and KPS score that were presented at initial diagnosis could precisely forecast the subsequent MT patterns of patients with LGG.

PIF7-mediated epigenetic reprogramming promotes the transcriptional response to shade in Arabidopsis.

For shade-intolerant plants, changes in light quality through competition from neighbors trigger shade avoidance syndrome (SAS): a series of morphological and physiological adaptations that are ultimately detrimental to plant health and crop yield. Phytochrome-interacting factor 7 (PIF7) is a major transcriptional regulator of SAS in Arabidopsis; however, how it regulates gene expression is not fully understood. Here, we show that PIF7 directly interacts with the histone chaperone anti-silencing factor 1 (ASF1). The ASF1-deprived asf1ab mutant showed defective shade-induced hypocotyl elongation. Histone regulator homolog A (HIRA), which mediates deposition of the H3.3 variant into chromatin, is also involved in SAS. RNA/ChIP-sequencing analyses identified the role of ASF1 in the direct regulation of a subset of PIF7 target genes. Furthermore, shade-elicited gene activation is accompanied by H3.3 enrichment, which is mediated by the PIF7-ASF1-HIRA regulatory module. Collectively, our data reveal that PIF7 recruits ASF1-HIRA to increase H3.3 incorporation into chromatin to promote gene transcription, thus enabling plants to effectively respond to environmental shade.

Shade-induced lncRNA PUAR promotes shade response by repressing PHYA expression.

Shade avoidance syndrome (SAS) commonly occurs in plants experiencing vegetative shade, triggering a series of morphological and physiological changes for the plants to reach more light. A number of positive regulators, such as PHYTOCHROME-INTERACTING 7 (PIF7), and negative regulators, such as PHYTOCHROMES, are known to ensure appropriate SAS. Here, we identify 211 shade-regulated long non-coding RNAs (lncRNAs) in Arabidopsis. We further characterize PUAR (PHYA UTR Antisense RNA), a lncRNA produced from the intron of the 5' UTR of the PHYTOCHROME A (PHYA) locus. PUAR is induced by shade and promotes shade-induced hypocotyl elongation. PUAR physically associates with PIF7 and represses the shade-mediated induction of PHYA by blocking the binding of PIF7 to the 5' UTR of PHYA. Our findings highlight a role for lncRNAs in SAS and provide insight into the mechanism of PUAR in regulating PHYA gene expression and SAS.

Association of high-sensitivity C-reactive protein and diabetic nephropathy in patients with type 2 diabetes: a Mendelian randomization study.

INTRODUCTION: Observational studies support the relationship between C-reactive protein (CRP) level and diabetic nephropathy (DN) in patients with diabetes. The research question regarding whether the relationship between serum high-sensitivity C-reactive protein (hsCRP) level and DN is causal lacks experimental evidence. Therefore, this study aimed to evaluate the causality between hsCRP and DN based on Mendelian randomization (MR) analysis. RESEARCH DESIGN AND METHODS: A total of 2332 participants with type 2 diabetes from the Taiwan Biobank database was analyzed. Genetic risk scores (GRSs), which comprise four validated CRP loci as two instrumental variables, were calculated as unweighted and weighted scores to evaluate the causal relationship of hsCRP with DN risk. The two-stage regression model was used to estimate OR and 95% CI. RESULTS: The analyses of the observational study showed that the hsCRP level was significantly associated with DN after multivariate adjustment (adjusted OR 1.15; 95% CI 1.01 to 1.32). Unweighted/weighted GRSs for log-transformed hsCRP satisfied MR assumptions 1 and 3, respectively; that is, a significant association with hsCRP was observed but that with DN was absent (adjusted OR 1.00, 95% CI 0.92 to 1.09; 1.00, 0.72 to 1.39, respectively). The MR analyses demonstrated that a 1-unit increase in the log-transformed genetically predicted hsCRP by unweighted and weighted GRSs was associated with DN, demonstrating ORs of 1.80 (95% CI 1.51 to 2.14) and 1.67 (95% CI 1.40 to 1.98), respectively. CONCLUSIONS: The current study provided experimental evidence that hsCRP level was causally related to DN. These findings suggest that the elevated hsCRP may be a causal risk factor for DN in patients with type 2 diabetes.

The sinuous, wave-like intratumoral-wall sign is a sensitive and specific radiological biomarker for oligodendrogliomas.

OBJECTIVES: The purpose of this study was to investigate the clinical utility of the sinuous, wave-like intratumoral-wall (SWITW) sign on T2WI in diagnosing isocitrate dehydrogenase (IDH) mutant and 1p/19q codeleted (IDHmut-Codel) oligodendrogliomas, for which a relatively conservative resection strategy might be sufficient due to a better response to chemoradiotherapy and favorable prognosis. METHODS: Imaging data from consecutive adult patients with diffuse lower-grade gliomas (LGGs, histological grades 2-3) in Beijing Tiantan Hospital (December 1, 2013, to October 31, 2021, BTH set, n = 711) and the Cancer Imaging Archive (TCIA) LGGs set (n = 117) were used to develop and validate our findings. Two independent observers assessed the SWITW sign and some well-reported discriminative radiological features to establish a practical diagnostic strategy. RESULTS: The SWITW sign showed satisfying sensitivity (0.684 and 0.722 for BTH and TCIA sets) and specificity (0.938 and 0.914 for BTH and TCIA sets) in defining IDHmut-Codels, and the interobserver agreement was substantial (κ 0.718 and 0.756 for BTH and TCIA sets). Compared to calcification, the SWITW sign improved the sensitivity by 0.28 (0.404 to 0.684) in the BTH set, and 81.0% (277/342) of IDHmut-Codel cases demonstrated SWITW and/ or calcification positivity. Combining the SWITW sign, calcification, low ADC values, and other discriminative features, we established a concise and reliable diagnostic protocol for IDHmut-Codels. CONCLUSIONS: The SWITW sign was a sensitive and specific imaging biomarker for IDHmut-Codels. The integrated protocol provided an explicable, efficient, and reproducible method for precise preoperative diagnosis, which was essential to guide individualized surgical plan-making. KEY POINTS: • The SWITW sign was a sensitive and specific imaging biomarker for IDHmut-Codel oligodendrogliomas. • The SWITW sign was more sensitive than calcification and an integrated strategy could improve diagnostic sensitivity for IDHmut-Codel oligodendrogliomas. • Combining SWITW, calcification, low ADC values, and other discriminative features could make a precise preoperative diagnosis for IDHmut-Codel oligodendrogliomas.

Risk prediction of nephropathy by integrating clinical and genetic information among adult patients with type 2 diabetes.

AIMS: Diabetic nephropathy (DN) is a major healthcare challenge. We developed and internally and externally validated a risk prediction model of DN by integrating clinical factors and SNPs from genes of multiple CKD-related pathways in the Han Chinese population. MATERIALS AND METHODS: A total of 1526 patients with type 2 diabetes were randomly allocated into derivation (n = 1019) or validation (n = 507) sets. External validation was performed with 3899 participants from the Taiwan Biobank. We selected 66 SNPs identified from literature review for building our weighted genetic risk score (wGRS). The steps for prediction model development integrating clinical and genetic information were based on the Framingham Heart Study. RESULTS: The AUROC (95% CI) for this DN prediction model with combined clinical factors and wGRS was 0.81 (0.78, 0.84) in the derivation set. Furthermore, by directly using the information of these 66 SNPs, our final prediction model had AUROC values of 0.85 (0.82, 0.87), 0.89 (0.86, 0.91), and 0.77 (0.74, 0.80) in the derivation, internal validation, and external validation sets, respectively. Under the combined model, the results with a cutoff point of 30% showed 70.91% sensitivity, 67.84% specificity, 51.54% positive predictive value, and 82.86% negative predictive value. CONCLUSIONS: We developed and internally and externally validated a model with clinical factors and SNPs from genes of multiple CKD-related pathways to predict DN in Taiwan. This model can be used in clinical risk management practice as a screening tool to identify persons who are genetically predisposed to DN for early intervention and prevention.

Alteration of default mode network: association with executive dysfunction in frontal glioma patients.

OBJECTIVE: Patients with frontal gliomas often experience executive dysfunction (EF-D) before surgery, and the changes in brain plasticity underlying this effect remain obscure. In this study, the authors aimed to assess whole-brain structural and functional alterations by using structural MRI and resting-state functional MRI (rs-fMRI) in frontal glioma patients with or without EF-D. METHODS: Fifty-seven patients with frontal gliomas were admitted prospectively to the authors' institution and assigned to one of two groups: 1) the normal executive function (EF-N) group and 2) the EF-D group, based on patient results for the Trail Making Test, Part B and Stroop Color-Word Test, Part C. Twenty-nine baseline-matched healthy controls were also recruited. All participants underwent multimodal MRI examination. Cortical surface thickness, surface-based resting-state activity (fractional amplitude of low-frequency fluctuation [fALFF] and regional homogeneity [ReHo]), and edge-based network functional connectivity (FC) were measured with FreeSurfer and fMRIPrep. The correlation between altered MRI parameters and executive function (EF) was assessed using Pearson correlation and receiver operating characteristic (ROC) analysis. RESULTS: Demographic characteristics (sex, age, and education level) and clinical characteristics (location, volume, grade of tumor, and preoperative epilepsy) were not significantly different between the groups, but the Karnofsky Performance Scale score was worse in the EF-D group. There was no significant difference in cortical surface thickness between the EF-D and EF-N groups. In both low-grade and high-grade glioma patients the fALFF value (permutation test + threshold-free cluster enhancement, p value after family-wise error correction < 0.05) and ReHo value (t-test, p < 0.001) of the left precuneus cortex in the EF-D group were greater than those in the EF-N group, which were negatively correlated with EF (p < 0.05) and enabled prediction of EF (area under the ROC curve 0.826 for fALFF and 0.855 for ReHo, p < 0.001). Compared with the EF-N group, the FCs between the default mode network (DMN) from DMN node to DMN node (DMN-DMN) and from the DMN to the central executive network (DMN-CEN) in the EF-D group were increased significantly (network-based statistics corrected p < 0.05) and negatively correlated with EF (Pearson correlation, p < 0.05). CONCLUSIONS: Apart from local disruption, the abnormally activated DMN in the resting state is related to EF-D in frontal glioma patients. DMN activity should be considered during preoperative planning and postoperative neurorehabilitation for frontal glioma patients to preserve EF. Clinical trial registration no.: NCT03087838 (ClinicalTrials.gov).

Nonhematogenic circulating aneuploid cells confer inferior prognosis and therapeutic resistance in gliomas.

Aneuploidy is the hallmark of malignancy. Our previous study successfully detected nonhematogenic circulating aneuploidy cells (CACs) in types of gliomas. The current prospective clinical study aims to further precisely subcategorize aneuploid CACs, including CD31- circulating tumor cells (CTCs) and CD31+ circulating tumor endothelial cells, and thoroughly investigate the clinical utilities of these different subtypes of cells. Co-detection and analysis of CTCs and circulating tumor-derived endothelial cells (CTECs) expressing CD133, glial fibrillary acidic protein (GFAP), or epidermal growth factor receptor variant III (EGFR vIII) were performed by integrated subtraction enrichment and immunostaining fluorescence in situ hybridization (SE-iFISH) in 111 preoperative primary diffuse glioma patients. Aneuploid CACs could be detected in most de novo glioma patients. Among detected CACs, 45.6% were CD31- /CD45- aneuploid CTCs and the remaining 54.4% were CD31+ /CD45- aneuploid CTECs. Positive detection of CTECs significantly correlated with disruption of the blood-brain barrier. The median number of large CTCs (L CTCs, >5 µm, 2) in low-grade glioma (WHO grade 2) was less than high-grade glioma (WHO grades 3 and 4) (3, p = 0.044), but this difference was not observed in small CTCs (S CTCs, ≤5 µm), CTECs or CACs (CTCs + CTECs). The numbers of CTCs, CTECs, or CACs in patients with contrast-enhancing (CE) lesions considerably exceeded that of non-CE lesions (p < 0.05). Receiver operating characteristic curves demonstrated that CD31+ CTECs, especially L CTECs, exhibited a close positive relationship with CE lesions. Survival analysis revealed that the high number of CD31- CTCs could be an adverse factor for compromised progression-free survival and overall survival. Longitudinal surveillance of CD31- CTCs was suitable for evaluating the therapeutic response and for monitoring potential emerging treatment resistance.

Orelabrutinib Combined With Lenalidomide and Immunochemotherapy for Relapsed/Refractory Primary Central Nervous System Lymphoma: A Retrospective Analysis of Case Series.

Background: Relapsed/refractory (r/r) primary central nervous system lymphoma (PCNSL) is an intractable situation without sound treatment. Bruton's tyrosine kinase (BTK) represents an attractive drug target in PCNSL. Orelabrutinib is a new-generation BTK inhibitor with high cerebrospinal fluid (CSF) concentration. This study aimed to evaluate the efficacy and safety of orelabrutinib-containing combination therapy in patients with r/r PCNSL. Methods: We retrospectively analyzed r/r PCNSL patients who received combination therapy with rituximab, high-dose methotrexate, temozolomide, orelabrutinib and lenalidomide, and further explored the relationship between the efficacy and genetic characteristics. Results: A total of fifteen patients were included in this retrospective study. The overall response rate (ORR) was 86.7%, the complete remission (CR) rate was 73.3% and the disease control rate (DCR) was 93.3%. Among 13 responders, 9 patients are still receiving oral orelabrutinib and lenalidomide. The most common adverse event (AEs) was transaminase increase (66.7%). No grade 4 AE or drug-related death was reported. Genomic sequencing showed that patients who responded to orelabrutinib had abnormal NF-κB activation, while those who had no response were mainly enriched with transcriptional misregulation. Patients who had mutations in TLR, BCR, or NF-κB pathway achieved complete or partial response to the orelabrutinib-containing therapy. Moreover, the blood and cerebrospinal fluid circulating tumor DNA (ctDNA) were closely associated with tumor recurrence and treatment response and sustained tumor responses correlated with the clearance of ctDNA. Conclusion: Orelabrutinib-containing regimen was effective and well-tolerated in patients with r/r PCNSL. Genome sequencing of tumor samples could help to screen patients who may respond to the orelabrutinib-containing regimen, and liquid biopsy may contribute to tracing tumor burden and monitoring treatment response.

T2/FLAIR Abnormity Could be the Sign of Glioblastoma Dissemination.

PURPOSE: Newly emerged or constantly enlarged contrast-enhancing (CE) lesions were the necessary signs for the diagnosis of glioblastoma (GBM) progression. This study aimed to investigate whether the T2-weighted-Fluid-Attenuated Inversion Recovery (T2/FLAIR) abnormal transformation could predict and assess progression for GBMs, especially for tumor dissemination. METHODS: A consecutive cohort of 246 GBM patients with regular follow-up and sufficient radiological data was included in this study. The series of T2/FLAIR and T1CE images were retrospectively reviewed. The patients were separated into T2/FLAIR and T1CE discordant and accordant subgroups based on the initial progression images. RESULTS: A total of 170 qualified patients were finally analyzed. The incidence of discordant T2/FLAIR and T1CE images was 25.9% (44/170). The median time-span of T2/FLAIR indicated tumor progression was 119.5 days (ranging from 57 days-unreached) prior to T1CE. Nearly half of patients (20/44, 45.5%) in the discordant subgroup suffered from tumor dissemination, substantially higher than accordant patients (23/126, 20.6%, p < 0.001). The median time to progression (TTP), post-progression survival (PPS), and overall survival (OS) were not statistically different (all p > 0.05) between discordant and accordant patients. CONCLUSIONS: T2/FLAIR abnormity could be the sign of GBM progression, especially for newly emerged lesions disseminating from the primary cavity. Physicians should cast more attention on the dynamic change of T2/FLAIR images, which might be of great significance for progression assessment and subsequent clinical decision-making.

Combining hyperintense FLAIR rim and radiological features in identifying IDH mutant 1p/19q non-codeleted lower-grade glioma.

OBJECTIVES: Even very small residual tumors of IDH mutant 1p/19q non-codeleted (IDHmut-Noncodel) astrocytoma could have a significantly negative impact on survival; thus, accurate preoperative diagnosis is of utmost importance to guide aggressive tumor resection strategy for this subtype. This study aimed to diagnose IDHmut-Noncodel from IDH mutant 1p/19q codeleted (IDHmut-Codel) and IDH wild-type gliomas by preoperative MRI and CT to guide surgical plan-making. METHODS: Consecutive adult patients diagnosed with diffuse lower-grade glioma (LGG, histological grade 2-3) from December 1, 2013 to December 31, 2020, were retrospectively included in this study. Clinical and radiological features were recorded and analyzed. Patients were divided into cohort A and cohort B for training and validation based on the operation date (2:1). RESULTS: A total of 585 patients were included in this study (cohort A, 390; cohort B, 195). The hyperintense FLAIR rim with hypointense core (hyperFLAIRrim) was a more sensitive sign than T2-FLAIR mismatch (T2FM) in defining IDHmut-Noncodel astrocytoma (sensitivity in cohort A: 0.713, 0.539, respectively; in cohort B: 0.713, 0.489, respectively) without compromised specificity (all 1.00). The hyperFLAIRrim, higher rADC, homogenous pattern on T2WI, non-calcification, and younger age were the most important factors associated with IDHmut-Noncodel astrocytoma. Combining these factors, the random forest model showed the best predictive ability. CONCLUSION: The hyperFLAIRrim sign was a specific and more sensitive sign in diagnosing IDHmut-Noncodel astrocytoma. Combining hyperFLAIRrim, higher rADC, homogenous pattern, non-calcification, and younger age could precisely predict glioma subtype for subsequent surgical plan-making. KEY POINTS: • A single hyperintense FLAIR rim (hyperFLAIRrim) sign with a hypointense core, regardless of T2 appearance, was more sensitive than T2FM in diagnosing IDHmut-Noncodel astrocytoma with high specificity. • The higher rADC value, homogenous pattern on T2WI, non-calcification, and younger age have a close relationship with IDHmut-Noncodel astrocytoma. • Neurosurgeons should perform a more aggressive resection strategy to prolong survival for radiologically indicated IDHmut-Noncodel astrocytoma. Our study provided a usable, practicable, and reliable protocol for neurosurgeons to make an individualized surgical strategy.

Unraveling the Dynamic Integration of Auxin, Brassinosteroid and Gibberellin in Early Shade-Induced Hypocotyl Elongation.

For shade-intolerant plants, a reduction in the red/far-red (R:FR) light ratio signals the close proximity of competitors and triggers shade-avoidance syndrome (SAS). Auxin, brassinosteroid, gibberellin and some transcriptional regulators have been reported to regulate shade-induced hypocotyl elongation. However, little is understood regarding the coordination of these multiple regulatory pathways. Here, combining time-lapse growth rates and transcriptomic data, we demonstrate that auxin and brassinosteroid affect two phases of shade-induced rapid growth, whereas gibberellin mainly contributes to the second rapid growth phase. PHYTOCHROME-INTERACTING FACTOR 7 (PIF7) acts earlier than other PIFs. PIF4 and PIF5 modulate the second rapid growth phase. LONG HYPOCOTYL IN FAR-RED 1 (HFR1) and PIF3-LIKE 1 (PIL1) modulate two rapid growth phases. Our results reveal that hormonal and transcriptional regulatory programs act together to coordinate dynamic hypocotyl changes in an immediate response to a shade signal and provide a novel understanding of growth kinetics in a changing environment. Supplementary Information: The online version contains supplementary material available at 10.1007/s43657-022-00044-3.

A prognostic estimation model based on mRNA-sequence data for patients with oligodendroglioma.

Background: The diagnosis of oligodendroglioma based on the latest World Health Organization Classification of Tumors of the Central Nervous System (WHO CNS 5) criteria requires the codeletion of chromosome arms 1p and 19q and isocitrate dehydrogenase gene (IDH) mutation (mut). Previously identified prognostic indicators may not be completely suitable for patients with oligodendroglioma based on the new diagnostic criteria. To find potential prognostic indicators for oligodendroglioma, we analyzed the expression of mRNAs of oligodendrogliomas in Chinese Glioma Genome Atlas (CGGA). Methods: We collected 165 CGGA oligodendroglioma mRNA-sequence datasets and divided them into two cohorts. Patients in the two cohorts were further classified into long-survival and short-survival subgroups. The most predictive mRNAs were filtered out of differentially expressed mRNAs (DE mRNAs) between long-survival and short-survival patients in the training cohort by least absolute shrinkage and selection operator (LASSO), and risk scores of patients were calculated. Univariate and multivariate analyses were performed to screen factors associated with survival and establish the prognostic model. qRT-PCR was used to validate the expression differences of mRNAs. Results: A total of 88 DE mRNAs were identified between the long-survival and the short-survival groups in the training cohort. Seven RNAs were selected to calculate risk scores. Univariate analysis showed that risk level, age, and primary-or-recurrent status (PRS) type were statistically correlated with survival and were used as factors to establish a prognostic model for patients with oligodendroglioma. The model showed an optimal predictive accuracy with a C-index of 0.912 (95% CI, 0.679-0.981) and harbored a good agreement between the predictions and observations in both training and validation cohorts. Conclusion: We established a prognostic model based on mRNA-sequence data for patients with oligodendroglioma. The predictive ability of this model was validated in a validation cohort, which demonstrated optimal accuracy. The 7 mRNAs included in the model would help predict the prognosis of patients and guide personalized treatment.

Refined Temporal-to-Frontal Horn Shunt for Treatment of Trapped Temporal Horn After Surgery of Peri- or Intraventricular Tumor: A Case Series Study.

BACKGROUND: Trapped temporal horn (TTH) is a localized hydrocephalus that can be treated with cerebrospinal fluid diversion. Refined temporal-to-frontal horn shunt (RTFHS) through the parieto-occipital approach is rarely reported in the literature and its effectiveness remains unclear. The aim of the present study is to investigate the efficacy and outcome of RTFHS for treatment of TTH. MATERIALS AND METHODS: We consecutively enrolled 10 patients who underwent RTFHS for TTH after surgical resection of peri- or intraventricular tumors from February 2018 to March 2021. Clinical, radiological, and follow-up data were collected and analyzed. The most common underlying pathology was meningioma (n=4), followed by central neurocytoma (n=3), thalamic glioblastoma (n=2), and anaplastic ependymoma (n=1). RESULTS: The mean Karnofsky performance scale (KPS) score and TTH volume at onset were 54.0 ± 15.1 (range 40-80) and 71.3 ± 33.2cm3 (range 31.7-118.6cm3), respectively. All patients (10/10, 100.0%) presented with periventricular brain edema (PVBE), while midline shift was observed in 9 patients (9/10, 90.0%). RTFHSs were implanted using valveless shunting catheters. No patients developed acute intracranial hemorrhage or new neurological deficit postoperatively. During the follow-up of 17.2 ± 13.7 months (range 3-39 months), all patients showed clinical and radiological improvement. The mean KPS score at the last follow-up was significantly increased to 88.0 ± 10.3 (range 70-100, p<0.0001). RTFHS resulted in significant complete remission in PVBE and midline shift in 8 (80.0%, p=0.0007) and 9 (100.0%, p=0.0001) patients, respectively. As the postoperative follow-up duration prolonged, the mean TTH volume decreased in a consistent, linear trend (p<0.0001). At last follow-up, the mean TTH volume was significantly reduced to 15.4 ± 11.5 cm3 (range 5.6-44.1 cm3, p=0.0003), resulting in a mean relative reduction of 77.2 ± 13.1% compared with the volume of TTH at onset. Over drainage was not observed during the follow-up. No patient suffered from proximal or distal shunt obstruction or shunt related infection, and the revision rate was 0%. CONCLUSION: RTFHS seems to be safe and effective for the treatment of TTH with favorable outcomes. Advantages of this technique could be technically less complex and invasive, cost-effective, avoidance of various intraperitoneal complications, and maintaining a near-physiological CSF pathway.

Nomograms for predicting cancer-specific survival in patients with primary central nervous system lymphoma: a population-based analysis.

BACKGROUND: This study identified the risk factors for survival in patients with primary central nervous system lymphoma (PCNSL). Nomograms were developed and validated to predict individualized overall survival (OS) and cancer-specific survival (CSS) in this particular cohort. METHODS: Patients diagnosed with PCNSL between 1975 and 2016 were selected from the Surveillance, Epidemiology, and End Results (SEER) database for this study. The Cox regression model, the Fine and Grey's model, and the backward method were applied to determine the risk factors for OS and CSS. Nomograms were established accordingly. Internal and external validation was performed in an Asian population to examine the accuracy of the nomograms. RESULTS: A total of 5,900 patients with PCNSL were identified from the SEER database. A further 163 patients with PCNSL from the Beijing Tiantan Hospital between 2004 and 2018 were included. Age at diagnosis, tumor site, pathological subtype, surgery, chemotherapy, coexisting malignancies, and HIV infection were independent risk factors of CSS. In addition to the risk factors of CSS, gender, marital status, and radiation were also independent factors of OS. Nomograms were developed to estimate the 1-, 3-, and 5-year OS and CSS. The discrimination and calibration of the nomograms performed well. The C-indexes of the nomograms for OS and CSS prediction were 0.728 [95% confidence interval (CI): 0.703-0.753] and 0.726 (95% CI: 0.696-0.756), respectively. In addition, compared with previously published OS nomograms, the newly established nomograms displayed superior prediction for OS. CONCLUSIONS: Nomograms predicting the 1-, 3- and 5-year OS and CSS of patients with PCNSL were established in this study. The validated nomograms showed relatively good performance and may be used clinically to evaluate patients' individualized risk and prognosis with PCNSL. Free software for individualized survival prediction is provided at http://www.pcnsl-survivalprediction.cn.

Corrigendum: Distinguishing Pseudoprogression From True Early Progression in Isocitrate Dehydrogenase Wild-Type Glioblastoma by Interrogating Clinical, Radiological and Molecular Features.

[This corrects the article DOI: 10.3389/fonc.2021.627325.].