bluuebunny/crossref_metadata_2025 huggingface dataset:
IMMU-07. TACEDINALINE (CI994), A CLASS I HDAC INHIBITOR, TARGETS INTRINSIC TUMOR GROWTH AND LEPTOMENINGEAL DISSEMINATION IN MYC-DRIVEN MEDULLOBLASTOMA WHILE MAKING THEM SUSCEPTIBLE TO ANTI-CD47 INDUCED MACROPHAGE PHAGOCYTOSIS VIA NF-KB-TGM2 DRIVEN TUMOR INFLAMMATION
Authors: Marquardt Viktoria , Theruvath Johanna , Qin Nan , Picard Daniel , Vibhakar Rajeev , Venkararaman Sujatha , Remke Marc , Mitra Siddhartha
Published: June 2023

BACKGROUND

While major advances have been made in improving the quality of life and survival of children with most forms of medulloblastoma (MB), those with MYC-driven tumors (Grp3-MB) still suffer significant morbidity and mortality. Here, we report a cross-entity, epigenetic drug screen to evaluate therapeutic vulnerabilities in MYC amplified medulloblastoma, which sensitizes them to macrophage-mediated phagocytosis upon targeting the CD47-SIRPa innate checkpoint pathway.

METHODS

We performed a primary screen including 78 epigenetic inhibitors and a secondary screen including 20 histone deacetylase inhibitors (HDACi) to compare response profiles in atypical teratoid/rhabdoid tumor (AT/RT, n=11), medulloblastoma (n=14), and glioblastoma (n=14). This unbiased approach revealed the preferential activity of HDACi in MYC-driven medulloblastoma. Importantly, the class I selective HDACi, CI-994, showed significant cell viability reduction mediated by induction of apoptosis in MYC-driven medulloblastoma, with little to no activity in non-MYC-driven medulloblastoma, AT/RT, and glioblastoma in vitro. We tested the combinatorial effect of targeting Class I HDACs and the CD47-SIRPa phagocytosis checkpoint pathway using in-vitro phagocytosis assays and in-vivo orthotopic xenograft models.

RESULTS

CI-994 displayed anti-tumoral effects at the primary site and the metastatic compartment in two orthotopic mouse models of MYC-driven medulloblastoma. Furthermore, RNA sequencing revealed NFκB pathway induction as a response to CI-994 treatment, followed by TGM2 expression, which enhanced inflammatory cytokine secretion. We further show interferon-gamma (IFN-g) release and cell surface expression of engulfment (“eat-me”) signals (such as calreticulin). Finally, combining CI-994 treatment with an anti-CD47 mAb targeting the CD47-SIRPa phagocytosis checkpoint enhanced in vitro phagocytosis and survival in tumor-bearing mice.

CONCLUSION

Together, these findings suggest a dynamic relationship between MYC amplification and innate immune suppression in MYC-amplified medulloblastoma and support further investigation of phagocytosis modulation as a strategy to enhance cancer immunotherapy responses.
LGG-14. TREATMENT OF TWO PEDIATRIC FGFR-ALTERED LOW-GRADE GLIONEURONAL TUMORS WITH MEK INHIBITION
Authors: Lazow Margot , Thomas Diana , Cottrell Catherine , Kobolt Daniel , Ramadesikan Swetha , Salloum Ralph , Shaikhouni Ammar , Mardis Elaine , Jones Jeremy , Leonard Jeffrey , Boué Daniel , Fouladi Maryam , Schieffer Kathleen
Published: June 2023

Somatic alterations in the fibroblast growth factor receptor (FGFR) gene family (FGFR1/2/3) have been implicated in tumorigenesis across pediatric low-grade glioneuronal neoplasms and represent a potential therapeutic target. FGFR rearrangements and internal tandem duplication (ITD) cause constitutive receptor tyrosine kinase activation, thereby promoting tumor cell growth, differentiation, and survival through complex downstream signaling, including via the mitogen activated protein kinase (MAPK) pathway. With increasing safety and efficacy data in pediatric neuro-oncology, MEK inhibitors may be considered to target MAPK pathway activation in FGFR-altered low-grade glioneuronal tumors, although clinical evidence within this specific molecular subgroup is lacking. Herein, we describe two cases of pediatric low-grade glioneuronal tumors harboring FGFR aberrations with encouraging clinical and radiographic response to MEK inhibition. The first patient has a multiply recurrent left parietal dysembryoplastic neuroepithelial tumor (DNET) with an FGFR1 ITD, diagnosed at eight years of age after presenting with seizures. Despite two surgical resections (with identical pathology), his disease slowly progressed. Oral MEK inhibitor therapy with trametinib was initiated, which he has remained on for the past 9+ months, with stable residual tumor without continued radiographic progression. The second patient was diagnosed at three years of age with focal epilepsy, prompting imaging demonstrating an infiltrative T2/FLAIR-hyperintense right temporal mass. Subtotal resection was performed, with pathology consistent with pediatric-type diffuse low-grade glioma. Molecular profiling identified an FGFR3-TACC3 fusion, with suspected enrichment for MAPK-pathway activation by preliminary RNA-sequencing analyses. Adjuvant therapy with trametinib was started, with small reduction in residual disease burden observed radiographically three months into treatment. Both patients continue on MEK inhibitor therapy with minimal toxicity and adequate control of underlying seizures. Though further research in larger, prospective cohorts with comprehensive biology data is necessary, oral MEK inhibitors represent a feasible and rational treatment consideration for pediatric FGFR-altered low-grade glioneuronal tumors.
LGG-20. LANDSCAPE OF FGFR ALTERATIONS IN PEDIATRIC AND AYA GLIOMAS
Authors: Nobre Liana , Sait Sameer Farouk , Bennet Julie , Larsen Alexandra Gianyini , Ho I-Chen , Gianno Francesca , Lin Andrew , Mellinghoff Ingo , Miller Alexandra , Siddaway Robert , Karijannis Matthias , Tabori Uri , Bale Tejus , Hawkins Cynthia
Published: June 2023

FGFR alterations including single nucleotide variants (SNV) and rearrangements represent common oncogenic alterations found in pediatric low-grade gliomas. From a population-based cohort of over 1800 pediatric and AYA (adolescent and young adult) gliomas, FGFR mutations were found in 6% of pediatric low-grade gliomas (LGG) and 16 % of IDH-WT AYA gliomas. Given the frequency of FGFR driver alterations, we assembled a large cohort of 370 FGFR mutated glioma across all ages (6 months to 87 years) 53% of which were LGG. In the pediatric patients, most (87%) of FGFR altered gliomas were low-grade; while in AYA patients only 67%. Fusions were more frequent in pediatric LGG (60%), while SNVs were more common in AYA LGG (57%). The rearranged genes also differed; pediatric LGG: 26% FGFR1 ITD, 20% FGFR1 fusions, 15% FGFR2 fusions. AYA LGG had equal frequency of FGFR1 and FGFR2 fusions (30%). In adults, high grade gliomas were more common (73%), and frequently had additional oncogenic drivers. In general, additional oncogenic drivers were more common with increasing age and grade. In contrast to pediatric and AYA LGG, FGFR3-TACC3 fusions represented 40% of adult cases. Interestingly, this fusion was also found in 10% of FGFR LGGs overall. Although analysis of clinical outcomes are still ongoing, in our preliminary data 18 patients with FGFR altered low grade gliomas were treated with targeted agents; 3 stopped due to toxicity and were not evaluated for response. From patients on MAPKi 1/6 had a minor response and 3/6 stable disease; while 6/9 on FGFRi had partial or minor responses with additional 3 patients recently initiated on the drug. FGFR alterations are frequently encountered in AYA and pediatric population, molecular characterization is important in guiding prognosis and therapy. Although encouraging, further studies are needed to assess the benefit of FGFR inhibition in these patients.
MDB-16. TARGETING EPIGENETIC DYSREGULATION IN PAEDIATRIC BRAIN TUMOURS
Authors: Badodi Sara , Marino Silvia
Published: June 2023

Medulloblastoma (MB) is the most common paediatric malignant brain tumour and is classified into four distinct molecular subgroups (WNT, SHH, G3 and G4), each of them further divided into subtypes with different prognosis and responses to therapy. Deregulation of chromatin modifier genes play an essential role in MB, particularly in the G4 subgroup. A BMI1High;CHD7Low molecular signature identifies patients with poor survival. We have shown that BMI1High;CHD7Low sustains MB growth through regulation of MAPK/ERK signalling and via epigenetic regulation of inositol metabolism in both G4 MB cells and patients. These tumours display over-activation of MAPK/ERK and AKT/mTOR pathways leading to energetic rewiring characterised by enhanced glycolytic capacity and reduced mitochondrial function. We demonstrate that inositol administration counteracts this metabolic alteration and significantly extends survival in an in vivo pre-clinical model. Additionally, we identify a synergistic vulnerability of G4 MB to a combination treatment with BMI1 and MAPK/ERK inhibitors that overcomes the acquired resistance induced by single drug therapies. Importantly, we have now analysed recurrent G4 MB and found that the BMI1High;CHD7Low signature is maintained at recurrence and it continues to predict the pharmacological vulnerabilities we previously described. Finally, we extended the analysis to other paediatric brain tumours, including histone mutant gliomas and ependymomas, and identified molecularly defined subgroups that exhibit differential response to the compounds predicted to be effective by the BMI1High;CHD7Low signature, hence expanding the spectrum of tumour potentially amenable to these novel pharmacological approaches.
MDB-26. CDK8 IS AN ONCOGENE IN GROUP 3 MEDULLOBLASTOMA THAT IMPACTS PROTEIN TRANSLATION BY REGULATING THE TRANSCRIPTIONAL ACTIVITY OF RIBOSOMAL GENES
Authors: Wang Dong , Veo Bethany , Pierce Angela , Ritz Caitlin , Vibhakar Rajeev
Published: June 2023

Medulloblastoma (MB) is one of the most common malignant childhood brain tumors. Single-cell RNA-seq analysis of human medulloblastoma patients revealed that Group 3 MBs are dominated by undifferentiated progenitor-like cells with elevated expression of ribosomal genes, suggesting that overactive ribosome biogenesis is a hallmark of Group 3 MB. Using CRISPR-Cas9 screen, we found that Cyclin-dependent kinase 8 (CDK8) is an essential gene for MYC MB viability. We showed that CDK8 facilitates MYC-driven transcriptional programs and is necessary for sustaining expression of MYC. Furthermore, the loss of CDK8 resulted in a reduction in the phosphorylation of RNA polymerase II CTD and caused significant changes in genome transcription. Using cut&run, we found CDK8 directly regulated ribosomal gene transcription activity. CDK8 inhibition impaired ribosome biosynthesis suppressed protein translation and led to a striking reduction in phospho-Pol II binding at the promoter regions and gene bodies of SE-associated genes. The combination of an mTOR inhibitor with CDK8 inhibitors showed remarkable synergy in suppressing ribosome biogenesis, decreasing cell viability and attenuating tumor growth in vitro and in multiple models of MB. This proposal outlines the mechanistic consequences of CDK8 inhibition on ribosome biogenesis and provides pre-clinical validation of CDK8 inhibitor treatment as a novel therapeutic approach in MYC MB.
MDB-27. A PRO-DRUG OF TRIPTOLIDE IN CLINICAL DEVELOPMENT ATTENUATES HIGH-RISK MEDULLOBLASTOMA GROWTH
Authors: Rodriguez-Blanco Jezabel , Salvador April , Suter Robert , Palomo-Caturla Isabel , Viera Megan , Nienhius Ashley Metts , Ayad Nagi , Robbins David
Published: June 2023

Medulloblastoma (MB), the most common malignant brain tumor of childhood, is currently classified in four major subgroups. A natural compound used in Chinese medicine for centuries, triptolide, has been shown to have a potent antitumor activity, and the efficacy of one of its derivatives is being evaluated in the clinic. However, to date no preclinical data supports the use of triptolide for the treatment of patients with MB. Here, we performed bioinformatic analyses to predict which subgroup of medulloblastoma patients would more likely benefit from the use of triptolide, and validated its efficacy in series of ex vivo and in vivo mouse and human derived MB models. Correlation analyses identified Group 3 (G3) MB patients as the most prone to respond to triptolide treatment. Consistent with this prediction, triptolide attenuated the growth of G3 MB at lower doses than those classified as SHH subgroup, increasing symptom-free survival in G3 mouse MB models. Transcriptomic analyses revealed MYC signaling as the key downstream target of triptolide in MB cells. Importantly, a pro-drug of triptolide in clinical development, minnelide, similarly showed efficacy in mouse and human derived G3 in vivo MB models. Our findings highlight the potential of repurposing Minnelide to treat G3 MB patients. Due to their dismal prognosis, inclusion of G3 MB patients in future minnelide clinical trials should be considered.
MDB-39. ASSESSMENT OF MEDULLOBLASTOMA PATIENTS THROUGH MONITORING EXTRACELLULAR VESICLES VIA SURFACE-ENHANCED RAMAN SPECTROSCOPY COMBINED WITH MACHINE LEARNING
Authors: Mata Carolina del Real , Lu Yao , Jalali Mahsa , Montermini Laura , Khatami Marjan , Danieau Geoffroy , Orozco Ana Castillo , Rak Janusz , Garzia Livia , Mahshid Sara
Published: June 2023

Medulloblastoma (MB) is the most common brain pediatric tumor associated with considerable morbidity. While MB is treated with multimodal approaches, including surgery, the currently available technologies fail to provide non-invasive access for continuous assessment of disease progression and therapy efficacy. There is a need to develop monitoring systems for frequent use with minimum invasiveness that provides actionable information incorporating the heterogeneous nature of MB. Liquid biopsy is a non-invasive approach using circulating biomarkers, including nano-sized extracellular vesicles (EVs). EVs are secreted by all cells, even cancerous ones. Molecular composition of cancer EVs contains fingerprints of their parental cell, reflective of salient features of the underlying disease. We used 54 pediatric plasma samples of MB patients to determine feasibility of assessing disease progression through EVs analysis. EVs were isolated from plasma using size exclusion chromatography prior to loading onto unique MoSERS chip. MoSERS platform contains nanostructured capture element for single EV detection capable of profiling liquid biopsy samples for surface-enhanced Raman Spectroscopy. A total of 54 datasets were generated, each comprised of EV spectra collected with the MoSERS chip at a single EV resolution. A spectral library was integrated with the datasets of patients with confirmed MB diagnosis (n=34) and healthy controls (n=20), required to train and test a machine-learning implementation. The combination of MoSERS with robust machine learning algorithm provides a strong analysis and a simple interpretation of the patient’s health status. We optimized a pipeline for the data collection and analysis, demonstrating the feasibility of the MoSERS platform for pediatric cancer indication and need for less than 10 μl of sample to generate each unique dataset. Preliminary results demonstrate that MoSERS performance correlates with the results of clinical standards, providing a proof-of-concept for its implementation as a non-invasive and accessible alternative to monitor the health status of MB patients.
MDB-40. TRANSCRIPTOME-BASED DRUG REPURPOSING IN GROUP 3 MEDULLOBLASTOMA
Authors: Doss David , Kanchan Ranjana , Perumal Naveenkumar , Batra Surinder , Mahapatra Sidharth
Published: June 2023

Medulloblastoma (MB) is the most common malignant pediatric brain tumor. MB is divided into four molecular subgroups (SHH, WNT, Group 3 [G3], and Group 4 [G4]), each defined by unique genetic and molecular features. G3MB is the most aggressive subgroup, with the lowest five-year survival. Features conferring high risk to G3MB include frequent metastases at diagnosis, MYC amplification, and chromosome i17q. Outcomes for G3MB patients remain dismal, partly due to a lack of G3MB-specific therapies, defining an important gap in MB research. To address this gap, we employed a strategy of comparing the G3MB transcriptomic signature against a repository of chemical perturbagens (LINCS) to identify FDA-approved, blood-brain barrier penetrant drugs capable of reverting the disease signature to a more normal cerebellum-like state. Following preliminary in silico and in vitro screening, we identified four drugs - fluoxetine, sertraline, simvastatin, and nortriptyline - that passed screening criteria and demonstrated cytotoxicity against HDMB03 cells at low micromolar doses. Each compound also inhibited clonogenicity, impaired wound healing, and impeded cell migration and invasion. Further, each compound induced apoptosis as evidenced by annexin V and propidium iodide staining. Western blotting confirmed both dose- and time-dependent increases in the expression of key apoptotic markers. Since nortriptyline possessed the best cytotoxicity profile against HDMB03 cells, we interrogated the transcriptome of HDMB03 cells treated with nortriptyline to identify cancer-related pathways inhibited by drug treatment. Our data revealed strong inhibition of E2F transcription factors, which are critical to cancer cell cycle progression and proliferation. Notably, five of the six E2F transcription factors as well as a panel of E2F target genes (HN1, KIF4A, CDCA3, CDCA8, and SSRP1) are all specifically upregulated in G3MB. This study highlights the promise of drug discovery and repurposing using subgroup-specific transcriptomes, which may deliver effective treatments expeditiously to high-risk patients.
XRT-07. LATE-ONSET LYMPHOPENIA DURING CRANIOSPINAL RADIATION IS ASSOCIATED WITH AN INCREASED RISK OF TUMOR RECURRENCE IN NEWLY-DIAGNOSED PEDIATRIC MEDULLOBLASTOMA
Authors: Lindsay Holly , Scheurer Michael , Allam Anthony , McGovern Susan , Chintagumpala Murali , Paulino Arnold
Published: June 2023

A recent publication (PMID 33556478) demonstrated an increased risk of tumor recurrence in patients with newly-diagnosed pediatric medulloblastoma who have decreased lymphocyte counts early in their course of craniospinal radiation (CSI) (weeks 1 and 2). We set out to confirm this data in an independent population of pediatric patients with newly-diagnosed medulloblastoma. We analyzed 54 patients treated from 1997-2013. All patients that received radiation in or after 2007 received protons. Per standard of care, patients with clinically high-risk disease were treated with 36-39.6 Gy CSI while patients with standard-risk disease received 23.4 Gy. Total dose to the primary site of disease ranged from 54-55.8 Gy. The mean patient age at diagnosis was 8 years. 16/54 (30%) patients developed a recurrence at an average of 30.2 months after diagnosis. Lymphocyte counts were analyzed both as a continuous variable and as CTCAE v5.0 grades (grades 0-2 lymphopenia (ALC >/=500) compared to grade 3 and 4 (ALC<500/mm3)) using Cox regression. As expected, patients with M+ disease had increased risk of tumor recurrence (p=0.001). There was no correlation between risk of tumor recurrence and early lymphopenia (weeks 0-3 radiation). However, in both weeks 4 and 5 of radiation, decreases in ALC closely correlated with an increased risk of tumor recurrence (week 4 p=0.038, week 5 p=0.042). Similarly, patients with grade 3/4 lymphopenia at weeks 4 and 5 of radiation had an increased risk of tumor recurrence (week 4 p=0.040, week 5 p=0.008) compared to those with grade 0-2 lymphopenia. In summary, both M+ disease and lymphopenia during weeks 4 and 5 of radiation correlated with an increased risk of tumor recurrence in pediatric medulloblastoma.
TRLS-16. RAPID GENERATION OF EPENDYMOMA MOUSE MODELS FOR PRE-CLINICAL STUDIES
Authors: Ippagunta Siri , Emanus Erik , Bertrand Kelsey , Mack Stephen
Published: June 2023

Pediatric Ependymomas are the leading cause of cancer death among children & adolescents with the 5-year progression free survival (PFS)rate being < 30%. Despite this poor prognosis there has been less success in development of targeted therapies. A major drawback in developing new therapeutics is lack of proper models of disease. Objective of out work has been to develop orthogonal models of various distinct groups of ependymoma to enable understanding of tumor microenvironment thus leading to strategies targeting potential therapeutic sites. In this regard we have developed two models of ZFTA-RELA Ependymoma: 1) In Utero Electroporation Model: DNA plasmids are transfected into developing forebrain, 2) Allograft Model: Primary tumor derived or in vitro transducer cells are allografted into various regions of brain. Further we have shown that these models molecularly resemble patient-derived tumors using RNA sequencing. Using these ZFTA-RELA mouse models we have shown that NSG mice (n=8/treatment group) treated with Selinexor (an XPO1 inhibitor) in combination with chemotherapy have lower tumor volumes by 40% as compared to vehicle or chemotherapy alone treated mice (P<0.05). Furthermore the combination therapy treated mice have improved survival by 28 days as compared to vehicle mice. In conclusion, we have shown that our novel models of ependymomas not only closely resemble disease in patients, but can also be used to develop effective targeted therapies.
foes or friends (1862)
Authors: Adams Henry
Published: June 2023

Of the year 1862 Henry Adams could never think without a shudder. The war alone did not greatly distress him; already in his short life he was used to seeing people wade in blood, and he could plainly discern in history, that man from...
political morality (1862)
Authors: Adams Henry
Published: June 2023

On Moran’s promotion to be Secretary, Mr. Seward inquired whether Minister Adams would like the place of Assistant Secretary for his son. It was the first—and last—office ever offered him, if indeed he could claim what was offered in fact to his father. To...
eccentricity (1863)
Authors: Adams Henry
Published: June 2023

Knowledge of human nature is the beginning and end of political education, but several years of arduous study in the neighborhood of Westminster led Henry Adams to think that knowledge of English human nature had little or no value outside of England. In Paris,...
chaos (1870)
Authors: Adams Henry
Published: June 2023

One fine May afternoon in 1870 Adams drove again up St. James’s Street wondering more than ever at the marvels of life. Nine years had passed since the historic entrance of May, 1861. Outwardly London was the same. Outwardly Europe showed no great change....
silence (1894–1898)
Authors: Adams Henry
Published: June 2023

The convulsion of 1893 left its victims in dead-water, and closed much education. While the country braced itself up to an effort such as no one had thought within its powers, the individual crawled as he best could, through the wreck, and found many...
II
Authors: Woolf Virginia
Published: June 2023

‘Mrs Flanders’ — ‘Poor Betty Flanders’ — ‘Dear Betty’ — ‘She’s very attractive still’ — ‘Odd she don’t marry again!’ ‘There’s Captain Barfoot to be sure — calls every Wednesday as regular as clockwork, and never brings his wife.’

‘But that’s Ellen Barfoot’s...
IV
Authors: Woolf Virginia
Published: June 2023

What’s the use of trying to read Shakespeare, especially in one of those little thin paper editions whose pages get ruffled, or stuck together with sea-water? Although the plays of Shakespeare had frequently been praised, even quoted, and placed higher than the Greek, never...
V
Authors: Woolf Virginia
Published: June 2023

‘I rather think,’ said Jacob, taking his pipe from his mouth, ‘it’s in Virgil,’ and pushing back his chair, he went to the window.

The rashest drivers in the world are, certainly, the drivers of post-office vans. Swinging down Lamb’s Conduit Street,*...
VIII
Authors: Woolf Virginia
Published: June 2023

About half-past nine Jacob left the house, his door slamming, other doors slamming, buying his paper, mounting his omnibus, or, weather permitting, walking his road as other people do. Head bent down, a desk, a telephone, books bound in green leather, electric light …...
X
Authors: Woolf Virginia
Published: June 2023

Through the disused graveyard in the parish of St Pancras,* Fanny Elmer strayed between the white tombs which lean against the wall, crossing the grass to read a name, hurrying on when the grave-keeper approached, hurrying into the street, pausing now by...
XIV
Authors: Woolf Virginia
Published: June 2023

‘He left everything just as it was,’ Bonamy marvelled. ‘Nothing arranged. All his letters strewn about for anyone to read. What did he expect? Did he think he would come back?’ he mused, standing in the middle of Jacob’s room.

The eighteenth century has...
Amy Foster
Authors: Conrad Joseph
Published: June 2023

Kennedy is a country doctor, and lives in Colebrook, on the shores of Eastbay.* The high ground rising abruptly behind the red roofs of the little town crowds the quaint High Street against the wall which defends it from the sea. Beyond the...
The Return
Authors: Conrad Joseph
Published: June 2023

The inner circle train* from the City rushed impetuously out of a black hole and pulled up with a discordant, grinding racket in the smirched twilight of a West-End station. A line of doors flew open and a lot of men stepped out...
I
Authors: Wharton Edith
Published: June 2023

A girl came out of Lawyer Royall’s house, at the end of the one street of North Dormer, and stood on the doorstep.

It was the beginning of a June afternoon. The spring-like transparent sky shed a rain of silver sunshine on the roofs of...
III
Authors: Wharton Edith
Published: June 2023

It was not in the room known at the red house as Mr. Royall’s office that he received his infrequent clients.

Professional dignity and masculine independence made it necessary that he should have a real office, under a different roof, and his standing as the...
VII
Authors: Wharton Edith
Published: June 2023

Since her reinstatement in Miss Hatchard’s favour Charity had not dared to curtail by a moment her hours of attendance at the library. She even made a point of arriving before the time, and showed a laudable indignation when the youngest Targatt girl, who...
VIII
Authors: Wharton Edith
Published: June 2023

She had lost the sense of time, and did not know how late it was till she came out into the street and saw that all the windows were dark between Miss Hatchard’s and the Royall house.

As she passed from under the black pall...
X
Authors: Wharton Edith
Published: June 2023

The lake at last—a sheet of shining metal brooded over by drooping trees. Charity and Harney had secured a boat, and, getting away from the wharves and the refreshment-booths, they drifted idly along, hugging the shadow of the shore. Where the sun struck the...
XV
Authors: Wharton Edith
Published: June 2023

That night, as usual, they said good-bye at the wood’s edge.

Harney was to leave the next morning early. He asked Charity to say nothing of their plans till his return, and, strangely even to herself, she was glad of the postponement. A leaden weight...
XVII
Authors: Wharton Edith
Published: June 2023

Charity lay on the floor on a mattress, as her dead mother’s body had lain. The room in which she lay was cold and dark and low-ceilinged, and even poorer and barer than the scene of Mary Hyatt’s earthly pilgrimage. On the other side...
XVIII
Authors: Wharton Edith
Published: June 2023

They began to jog down the winding road to the valley at old Dan’s languid pace. Charity felt herself sinking into deeper depths of weariness, and as they descended through the bare woods there were moments when she lost the exact sense of things,...
Swann in Love
Authors: Nelson Brian
Published: June 2023

To belong to the ‘little set’, the ‘little circle’, the ‘little clan’ of the Verdurins, one condition was sufficient but necessary: tacit adherence to a Credo one of whose articles was that the young pianist who was Madame Verdurin’s protégé that year and of...
Paris: September 1792
Authors: Orczy Baroness
Published: June 2023

A surging, seething, murmuring crowd, of beings that are human only in name, for to the eye and ear they seem naught but savage creatures, animated by vile passions and by the lust of vengeance and of hate. The hour, some little time before...
The Accredited Agent
Authors: Orczy Baroness
Published: June 2023

The afternoon was rapidly drawing to a close; and a long, chilly English summer’s evening was throwing a misty pall over the green Kentish landscape.

The Day Dream had set sail, and Marguerite Blakeney stood alone on the edge of the cliff for...
The Scrap of Paper
Authors: Orczy Baroness
Published: June 2023

Marguerite suffered intensely. Though she laughed and chatted, though she was more admired, more surrounded, more fêted than any woman there, she felt like one condemned to death, living her last day upon this earth.

Her nerves were in a state of painful tension, which...
Either—or?
Authors: Orczy Baroness
Published: June 2023

The few words which Marguerite Blakeney had managed to read on the half-scorched piece of paper, seemed literally to be the words of Fate. ‘Start myself to-morrow….’ This she had read quite distinctly; then came a blur caused by the smoke of the candle,...
The Death-Trap
Authors: Orczy Baroness
Published: June 2023

The next quarter of an hour went by swiftly and noiselessly. In the room downstairs, Brogard had for a while busied himself with clearing the table, and re-arranging it for another guest.

It was because she watched these preparations, that Marguerite found the time slipping...
The Jew
Authors: Orczy Baroness
Published: June 2023

It took Marguerite some time to collect her scattered senses; the whole of this last short episode had taken place in less than a minute, and Desgas and the soldiers were still about two hundred yards away from the ‘Chat Gris.’

When she realized what...
Scoutcraft
Authors: Baden-Powell Robert
Published: June 2023

Notes for Instructor

The following is a suggestion for the distribution of the work for the first week. It is merely a suggestion and in no sense binding.

First Evening:

Indoors

Address the boys on ‘Scoutcraft’, giving a summary of the whole scheme, as...
ENDURANCE for SCOUTS; or , How to be Strong
Authors: Baden-Powell Robert
Published: June 2023

Camp Fire Yarn.—No. 17

How to Grow Strong

Need for Scouts to be strong—Exercises—Care of Body—Nose—Ears—Eyes—Teeth—Practices.

A Scout’s Endurance

A scout lay sick in hospital in India with that most fatal disease called cholera. The doctor told the native man in attendance on him...
Chivalry of the Knights
Authors: Baden-Powell Robert
Published: June 2023

Hints to Instructors

One aim of the Boy Scouts scheme is to revive amongst us, if possible, some of the rules of the knights of old, which did so much for the moral tone of our race, just as the Bushido of the ancient Samurai...
Scouting Games, Practices, and Displays
Authors: Baden-Powell Robert
Published: June 2023

Notes to Instructors

Instruction in scouting should be given as far as possible through practices, games, and competitions.

Games should be organised mainly as team matches, where the patrol forms the team, and every boy is playing, none merely looking on.

Strict obedience...
Kew Gardens
Authors: Woolf Virginia
Published: June 2023

From the oval shaped flower-bed there rose perhaps a hundred stalks spreading into heart shaped or tongue shaped leaves half way up and unfurling at the tip red or blue or yellow petals marked with spots of colour raised upon the surface; and from...
Solid Objects
Authors: Woolf Virginia
Published: June 2023

The only thing that moved upon the vast semi-circle of the beach was one small black spot. As it came nearer to the ribs and spine of the stranded pilchard boat,* it became apparent from a certain tenuity in its blackness that...
Blue & Green
Authors: Woolf Virginia
Published: June 2023

Blue

The snub-nosed monster rises to the surface and spouts through his blunt nostrils two columns of water, which, fiery-white in the centre, spray off into a fringe of blue beads. Strokes of blue line the black tarpaulin of his hide. Slushing the water...
In The Orchard
Authors: Woolf Virginia
Published: June 2023

Miranda slept in the orchard, lying in a long chair beneath the apple tree. Her book had fallen into the grass, and her finger still seemed to point at the sentence ‘Ce pays est vraiment un des coins du monde où le rire...
‘Slater’s Pins Have No Points’
Authors: Woolf Virginia
Published: June 2023

‘Slater’s pins have no points — don’t you always find that?’ said Miss Craye, turning round as the rose fell out of Fanny Wilmot’s dress, and Fanny stooped with her ears full of the music, to look for the pin on the floor.

The words gave her...
The Lady in the Looking-Glass: A Reflection
Authors: Woolf Virginia
Published: June 2023

People should not leave looking-glasses hanging in their rooms any more than they should leave open cheque books or letters confessing some hideous crime. One could not help looking, that summer afternoon, in the long glass that hung outside in the hall. Chance had...
Amory, Son of Beatrice
Authors: Fitzgerald F. Scott
Published: June 2023

Amory Blaine inherited from his mother every trait, except the stray inexpressible few, that made him worth while. His father, an ineffectual, inarticulate man with a taste for Byron* and a habit of drowsing over the Encyclopædia Britannica, grew wealthy...
The Egotist Considers
Authors: Fitzgerald F. Scott
Published: June 2023

“Ouch! Let me go!”

He dropped his arms to his sides.

“What’s the matter?”

“Your shirt stud—it hurt me—look!” She was looking down at her neck, where a little blue spot about the size of a pea marred its pallor.

“Oh, Isabelle,” he...
The Débutante
Authors: Fitzgerald F. Scott
Published: June 2023

The time is February. The place is a large, dainty bedroom in the Connage house on Sixty-eighth Street, New York. A girl’s room: pink walls and curtains and a pink bedspread on a cream-colored bed. Pink and cream are the motifs of the room, but...
Young Irony
Authors: Fitzgerald F. Scott
Published: June 2023

For years afterward when Amory thought of Eleanor he seemed still to hear the wind sobbing around him and sending little chills into the places beside his heart. The night when they rode up the slope and watched the cold moon float through the...
The Supercilious Sacrifice
Authors: Fitzgerald F. Scott
Published: June 2023

Atlantic City.* Amory paced the board walk at day’s end, lulled by the everlasting surge of changing waves, smelling the half-mournful odor of the salt breeze. The sea, he thought, had treasured its memories deeper than the faithless land. It seemed still...
Mary Wollstonecraft Shelley
Authors: Shelley Mary Wollstonecraft
Published: June 2023

July 16, 1833.—This is a memorable anniversary for me; on it I complete my three hundred and twenty-third year!

The Wandering Jew?*—certainly not. More than eighteen centuries have passed over his head. In comparison with him, I am a very young Immortal.

Am...
Edgar Allan Poe
Authors: Poe Edgar Allan
Published: June 2023

Πυρ σοι προσισω

I will bring fire to thee.

Euripides—Androm:*
Jack London
Authors: London Jack
Published: June 2023

There it was! The abrupt liberation of sound, as he timed it with his watch, Bassett likened to the trump of an archangel. Walls of cities, he meditated, might well fall down before so vast and compelling a summons.* For the thousandth...
PORTRAIT OF A SIREN
Authors: Fitzgerald F. Scott
Published: June 2023

Crispness folded down upon New York a month later, bringing November and the three big football games* and a great fluttering of furs along Fifth Avenue. It brought, also, a sense of tension to the city, and suppressed excitement. Every morning now...
THE BROKEN LUTE
Authors: Fitzgerald F. Scott
Published: June 2023

It is seven-thirty of an August evening. The windows in the living-room of the gray house are wide open, patiently exchanging the tainted inner atmosphere of liquor and smoke for the fresh drowsiness of the late hot dusk. There are dying flower scents upon the...
A MATTER OF ÆSTHETICS
Authors: Fitzgerald F. Scott
Published: June 2023

On the night when Anthony had left for Camp Hooker one year before, all that was left of the beautiful Gloria Gilbert — her shell, her young and lovely body — moved up the broad marble steps of the Grand Central Station with the rhythm of the engine...
NO MATTER!
Authors: Fitzgerald F. Scott
Published: June 2023

Within another year Anthony and Gloria had become like players who had lost their costumes, lacking the pride to continue on the note of tragedy — so that when Mrs. and Miss Hulme of Kansas City cut them dead in the Plaza one evening, it was...
3
Authors: Arnim Elizabeth Von
Published: June 2023

The owner of the mediaeval castle was an Englishman, a Mr. Briggs, who was in London at the moment and wrote that it had beds enough for eight people, exclusive of servants, three sitting-rooms, battlements, dungeons, and electric light. The rent was £60 for...
4
Authors: Arnim Elizabeth Von
Published: June 2023

It had been arranged that Mrs. Arbuthnot and Mrs. Wilkins, travelling together, should arrive at San Salvatore on the evening of March 31st — the owner, who told them how to get there, appreciated their disinclination to begin their time in it on April 1st — and Lady...
6
Authors: Arnim Elizabeth Von
Published: June 2023

When Mrs. Wilkins woke next morning she lay in bed a few minutes before getting up and opening the shutters. What would she see out of her window? A shining world, or a world of rain? But it would be beautiful; whatever it was...
8
Authors: Arnim Elizabeth Von
Published: June 2023

Presently, when Mrs. Wilkins and Mrs. Arbuthnot, unhampered by any duties, wandered out and down the worn stone steps and under the pergola into the lower garden, Mrs. Wilkins said to Mrs. Arbuthnot, who seemed pensive, ‘Don’t you see that if somebody else does...
14
Authors: Arnim Elizabeth Von
Published: June 2023

That first week the wistaria began to fade, and the flowers of the Judas-tree and peach-trees fell off and carpeted the ground with rose-colour. Then all the freesias disappeared, and the irises grew scarce. And then, while these were clearing themselves away, the double...
19
Authors: Arnim Elizabeth Von
Published: June 2023

And then when she spoke … what chance was there for poor Briggs? He was undone. All Scrap said was, ‘How do you do,’ on Mr. Wilkins presenting him, but it was enough: it undid Briggs.

From a cheerful, chatty, happy young man, overflowing with...
Arrival
Authors: Kafka Franz
Published: June 2023

It was late evening when K. arrived. The village lay deep in snow. There was nothing to be seen of Castle Mount, for mist and darkness surrounded it, and not the faintest glimmer of light showed where the great castle lay. K. stood on...
Barnabas
Authors: Kafka Franz
Published: June 2023

The three of them were sitting rather silently at a small table in the saloon bar of the inn over their beer, K. in the middle, his assistants to right and left of him. Otherwise there was only a table where some of the...
Frieda
Authors: Kafka Franz
Published: June 2023

In the bar, a large room entirely empty in the middle, several men were sitting around the walls, near and on casks, but they looked different from the local rustics in K.’s inn. They were more neatly dressed, all of them wearing clothes of...
The Teacher
Authors: Kafka Franz
Published: June 2023

K. found the teacher up there. It was good to see that the room could hardly be recognized, Frieda had been so busy. It had been well aired, the stove heated with plenty of fuel, the floor washed, the bed made, while the...
Opposition to Questioning
Authors: Kafka Franz
Published: June 2023

He tore himself away and went back into the building, not along the wall this time, but through the middle of the snow. In the entrance hall he met the landlord, who greeted him in silence and pointed to the door of the bar,...
At the School
Authors: Kafka Franz
Published: June 2023

He reached home frozen. It was dark everywhere, the candles in the lanterns had burned down, and he made his way into one of the classrooms with the help of the assistants, who knew their way around the place—‘Your first praiseworthy job done,’ he...
Frieda’s Grievance
Authors: Kafka Franz
Published: June 2023

Hans had left none too soon, for next moment the teacher opened the door and cried, on seeing K. and Frieda sitting quietly at the table: ‘Oh, pray forgive me for disturbing you! But can you tell me when you are finally going to...
At Amalia’s House
Authors: Kafka Franz
Published: June 2023

At last—it was already dark, late in the afternoon—K. had cleared the garden path, piling up the snow and beating it down firmly on both sides of the path, and now he had finished his day’s work. He stood at the garden gate, with...
Amalia’s Secret
Authors: Kafka Franz
Published: June 2023

‘Judge for yourself,’ said Olga, ‘and by the way, it sounds very simple, so you may not understand at once what great significance it can have. There’s an official at the castle called Sortini.’* ‘Oh, I’ve heard of him before,’ said...
Amalia’s Punishment
Authors: Kafka Franz
Published: June 2023

‘But soon afterwards questions were being fired at us from all sides about that letter. Friends and enemies called to see us, acquaintances and strangers, but no one stayed long. Our best friends were in more of a hurry than anyone to say...
Olga’s Plans
Authors: Kafka Franz
Published: June 2023

‘Now we had to find some occupation for our father that he could still manage, something that would at least keep him believing that it helped to lift the blame from our family. Finding anything like that was not easy, basically everything I...
The Arrest
Authors: Kafka Franz
Published: June 2023

Someone must have been telling tales about Josef K., for one morning, without having done anything wrong, he was arrested.* Frau Grubach’s cook, who brought him his breakfast at around eight every day, did not appear. That had never happened before. For...
Going To See Elsa
Authors: Kafka Franz
Published: June 2023

One evening, shortly before going home, K. received a telephone call summoning him to the court offices. He was warned, the voice said, not to disobey.* His outrageous remarks that the hearings were pointless, that they produced no result and never would,...
Going To See His Mother
Authors: Kafka Franz
Published: June 2023

During lunch it suddenly occurred to him that he ought to go and see his mother. Spring was almost over, and with it the third year since he had last seen her. On that occasion she had asked him to come and visit her...
In the Penal Colony
Authors: Kafka Franz
Published: June 2023

‘It is a remarkable apparatus,’ said the officer to the enquiring traveller,* surveying the apparatus with some admiration in his eyes, though it must have been long familiar to him. It seemed that it was only out of courtesy that the...
Letter to his Father
Authors: Kafka Franz
Published: June 2023

Schelesen*

Dearest Father,

You asked me once recently why it is I maintain I am afraid of you. As usual, I wasn’t able to give you any answer, partly on account of that very fear, partly because if I am to explain the reasons...
Mrs Dalloway
Authors: Woolf Virginia
Published: June 2023

Mrs Dalloway said she would buy the flowers herself.

For Lucy had her work cut out for her. The doors would be taken off their hinges; Rumpelmayer’s* men were coming. And then, thought Clarissa Dalloway, what a morning—fresh as if issued to children...
Chapter III
Authors: Conrad Joseph
Published: June 2023

A marvellous stillness pervaded the world, and the stars, together with the serenity of their rays, seemed to shed upon the earth the assurance of everlasting security. The young moon recurved, and, shining low in the west, was like a slender shaving thrown up...
Chapter V
Authors: Conrad Joseph
Published: June 2023

“Oh yes. I attended the inquiry,” he would say, “and to this day I haven’t left off wondering why I went. I am willing to believe each of us has a guardian angel, if you fellows will concede to me that each of...
Chapter VI
Authors: Conrad Joseph
Published: June 2023

“The authorities were evidently of the same opinion. The inquiry was not adjourned. It was held on the appointed day to satisfy the law, and it was well attended because of its human interest no doubt. There was no incertitude as to facts—as...
Chapter VII
Authors: Conrad Joseph
Published: June 2023

“An outward-bound mail-boat had come in that afternoon, and the big dining-room of the hotel was more than half full of people with a hundred pounds round-the-world tickets in their pockets. There were married couples looking domesticated and bored with each other in...
Chapter X
Authors: Conrad Joseph
Published: June 2023

“He locked his fingers together and tore them apart. Nothing could be more true: he had indeed jumped into an everlasting deep hole. He had tumbled from a height he could never scale again. By that time the boat had gone driving forward...
Chapter XIII
Authors: Conrad Joseph
Published: June 2023

“After these words, and without a change of attitude, he, so to speak, submitted himself passively to a state of silence. I kept him company; and suddenly, but not abruptly, as if the appointed time had arrived for his moderate and husky voice...
Chapter XIV
Authors: Conrad Joseph
Published: June 2023

“I slept little, hurried over my breakfast, and after a slight hesitation gave up my early morning visit to my ship. It was really very wrong of me, because, though my chief mate was an excellent man all round, he was the victim...
Chapter XVI
Authors: Conrad Joseph
Published: June 2023

“The time was coming when I should see him loved, trusted, admired, with a legend of strength and prowess forming round his name as though he had been the stuff of a hero. It’s true—I assure you; as true as I’m sitting here...
Chapter XX
Authors: Conrad Joseph
Published: June 2023

“Late in the evening I entered his study, after traversing an imposing but empty dining-room very dimly lit. The house was silent. I was preceded by an elderly grim Javanese servant in a sort of livery of white jacket and yellow sarong, who,...
Chapter XXIII
Authors: Conrad Joseph
Published: June 2023

“He did not return till next morning. He had been kept to dinner and for the night. There never had been such a wonderful man as Mr Stein. He had in his pocket a letter for Cornelius (‘the Johnnie who’s going to get...
Chapter XXXVII
Authors: Conrad Joseph
Published: June 2023

“It all begins with a remarkable exploit of a man called Brown, who stole with complete success a Spanish schooner out of a small bay near Zamboanga. Till I discovered the fellow my information was incomplete, but most unexpectedly I did come upon...
Chapter XXXVIII
Authors: Conrad Joseph
Published: June 2023

“It all begins, as I’ve told you, with the man called Brown,”* ran the opening sentence of Marlow’s narrative. “You who have knocked about the Western Pacific must have heard of him. He was the show ruffian on the Australian coast—not...
The After-Thought
Authors: Du Bois W. E. B.
Published: June 2023

Hear my cry, O God the Reader; vouchsafe that this my book fall not still-born into the world-wilderness. Let there spring, Gentle One, from out its leaves vigor of thought and thoughtful deed to reap the harvest wonderful. (Let the ears of a guilty people...
CHAPTER II
Authors: Fitzgerald F. Scott
Published: June 2023

About half way between West Egg and New York the motor road hastily joins the railroad and runs beside it for a quarter of a mile, so as to shrink away from a certain desolate area of land. This is a valley of ashes—a...
CHAPTER VI
Authors: Fitzgerald F. Scott
Published: June 2023

About this time an ambitious young reporter from New York arrived one morning at Gatsby’s door and asked him if he had anything to say.

“Anything to say about what?” inquired Gatsby politely.

“Why—any statement to give out.”

It transpired after a confused five minutes...
CHAPTER VII
Authors: Fitzgerald F. Scott
Published: June 2023

IT was when curiosity about Gatsby was at its highest that the lights in his house failed to go on one Saturday night—and, as obscurely as it had begun, his career as Trimalchio* was over. Only gradually did I become aware that the...