bluuebunny/crossref_metadata_2025 huggingface dataset:
Temporal trends in the utilization of advanced therapies among patients with acute pulmonary embolism: insights from a national database
Authors: Abumoawad Abdelrhman , Shatla Islam , Behrooz Leili , Eberhardt Robert T , Hamburg Naomi , Sedhom Rami , Elgendy Islam Y , Kumbhani Dharam J , Cameron Scott J , Elbadawi Ayman
Published: August 2023

There is a paucity of data regarding the contemporary temporal trends in the adoption of advanced pulmonary embolism (PE) therapies in the United States as well as the parallel trends in outcomes of patients with acute PE. Therefore, we queried the Nationwide Readmissions Database (years 2016–2020) to report the temporal trends in utilization of advanced PE therapies. Our final analysis included 920 770 hospitalizations with acute PE. We demonstrated an increase in the proportion of patients diagnosed with high-risk PE during the study years. Overall, there was an increase in the use of advanced PE therapies, which was mainly due to the increase in the utilization of systemic thrombolytics, and catheter-directed therapies. Also, extracorporeal membrane oxygenation cannulation showed an incremental increase over the study years. The use of inferior vena cava filter has declined, while the use of surgical embolectomy did not change during the study years. The use of advanced therapies has increased among urban teaching, but not among urban non-teaching hospitals. During the study years, there was no change in unadjusted or adjusted in-hospital mortality rates among patients with acute PE, while the 90-day unplanned readmission rate has declined.
Outcome of mitral repair combined with Cox-maze procedure for atrial functional mitral regurgitation with heart failure with recovered ejection fraction
Authors: Ye Qing , Zhao Yichen , Bai Chen , Liu Kemin , Zhao Cheng , Liu Yang , Li Yuqi , Wang Jiangang
Published: August 2023

OBJECTIVES

Atrial functional mitral regurgitation (AFMR) in patients with heart failure with recovered ejection fraction has received insufficient attention. This study analysed the prognosis and outcomes of mitral valve (MV) repair combined with the Cox-maze procedure.

METHODS

A prospective cohort study of patients with AFMR with left ventricular ejection fraction (LVEF) <40% was conducted. All patients received guideline-directed medical therapy. Those with recovered ejection fraction underwent MV repair combined with the Cox-maze procedure. Mortality, atrial fibrillation (AF) recurrence, mitral regurgitation (MR) and postoperative tricuspid regurgitation were assessed using the inverse probability weighting (IPW) method.

RESULTS

In total, 312 patients were enrolled in this study between 2010 and 2019, 247 of whom underwent MV repair combined with the Cox-maze procedure [full recovery (LVEF > 50%): n = 132, partial recovery (LVEF of 40–50%): n = 115]. IPW-adjusted survival of patients with LVEF ≥50% and LVEF 40–50% showed no significant difference [hazard ratio (HR): 2.18, 95% confidence interval: 0.46–10.38, P = 0.33]. However, patients with LVEF ≥50% had better IPW-adjusted long-term freedom from recurrent MR [HR: 2.44 (1.28–4.63), P = 0.0065] and AF recurrence [HR: 1.85 (1.06–3.21), P = 0.030] than those with LVEF of 40–50%.

CONCLUSIONS

MV repair combined with the Cox-maze procedure was effective and feasible in patients with severe AFMR with heart failure with recovered ejection fraction. Additionally, patients with LVEF ≥50% after guideline-directed medical therapy undergoing these combined procedures had better long-term freedom from recurrent AF and MR than those with LVEF of 40–50%.
Propagator and transfer matrices, Marchenko focusing functions and their mutual relations
Authors: Wapenaar Kees , Dukalski Marcin , Reinicke Christian , Snieder Roel
Published: August 2023

Many seismic imaging methods use wavefield extrapolation operators to redatum sources and receivers from the surface into the subsurface. We discuss wavefield extrapolation operators that account for internal multiple reflections, in particular propagator matrices, transfer matrices and Marchenko focusing functions. A propagator matrix is a square matrix that ‘propagates’ a wavefield vector from one depth level to another. It accounts for primaries and multiples and holds for propagating and evanescent waves. A Marchenko focusing function is a wavefield that focuses at a designated point in space at zero time. Marchenko focusing functions are useful for retrieving the wavefield inside a heterogeneous medium from the reflection response at its surface. By expressing these focusing functions in terms of the propagator matrix, the usual approximations (such as ignoring evanescent waves) are avoided. While a propagator matrix acts on the full wavefield vector, a transfer matrix (according to the definition used in this paper) ‘transfers’ a decomposed wavefield vector (containing downgoing and upgoing waves) from one depth level to another. It can be expressed in terms of decomposed Marchenko focusing functions. We present propagator matrices, transfer matrices and Marchenko focusing functions in a consistent way and discuss their mutual relations. In the main text we consider the acoustic situation and in the appendices we discuss other wave phenomena. Understanding these mutual connections may lead to new developments of Marchenko theory and its applications in wavefield focusing, Green’s function retrieval and imaging.
Expanding and Contracting the UN Guiding Principles: an Analysis of Recent Inter-American Human Rights Court Decisions
Authors: Smart Sebastián
Published: August 2023

In 2021, the Inter-American Court of Human Rights (IACtHR) decided two cases for advancing the increasing jurisprudence on the implementation of human rights and business standards, yet there is still a gap to fill. Despite the important development with regards to the State obligation to supervise business operations, the decisions do not introduce further definitions of companies’ responsibilities on human rights nor the potential of creating mandatory remedies standards for private agents. Through the analysis of the 2021 case law, this article concludes that the IACtHR has been increasingly using the UN Guiding Principles to argue for its rulings but has missed the opportunity to generate greater accountability for companies and private actors in its decision-making.
Surgical approach to coexistent inguinal endometriosis and inguinal hernial defect: a case report
Authors: Almagushi Nouf , Almadhi Leen , Aljomah Nadia , Albabtain Ibrahim
Published: August 2023

The presence of ectopic endometrial and myometrial tissue is referred to as endometriosis. The majority of cases of inguinal endometriosis are linked to prior uterine surgery. We present a 39-year-old female presented to the general surgery clinic in June 2013 with mild right inguinal pain and swelling. Enhanced computed tomography scan of the abdominal and pelvis revealed an elongated cystic mass in the right groin region. Diagnostic laparoscopy was performed and the uterus, both ovaries, and pouch of Douglas were examined. Two endometrial deposits were detected: on in the superoposteriar part of the uterus and another below the base of the right fallopian tube. In addition to the right inguinal hernia, a cystic lesion was noted on the surface of the round ligament. The entire round ligament, including the canal of Nuck, and cyst were dissected and excised completely. The right inguinal hernia was repaired.
Pleomorphic dermal sarcoma: it might be rare but it exists
Authors: Seretis Konstantinos , Klaroudas Antonios , Galani Vasiliki , Papathanakos Georgios , Varouktsi Anna , Mitselou Antigoni , Batistatou Anna , Lampri Evangeli
Published: August 2023

Pleomorphic dermal sarcoma (PDS) is a rare mesenchymal tissue tumor. Its differential diagnosis from similar tumors, such as low differentiated squamous cell carcinoma, fibrosarcoma, desmoplastic melanoma, atypical fibroxanthoma (AFX), may be difficult, as they have similar clinical and histological presentation. We present a case of an 83-year-old man exhibiting an exophytic scalp lesion. Excision of the lesion was performed, ensuring clear surgical margins and pathologic examination revealed an invasive pleomorphic dermal sarcoma. This case highlights a rare case of a large pleomorphic dermal sarcoma, and it discusses the histological, molecular features, its differential diagnosis and management of PDS.
Surgical management of isolated caecal varices presenting with massive lower gastrointestinal haemorrhage: a case report and review of the literature
Authors: Qian Wanyang , Mac Curtain Benjamin M , Trivedi Anand
Published: August 2023

Caecal varices are extremely rare with poorly defined management due to paucity of data. A 52-year-old man was diagnosed with a 3-day history of melena with a background of chronic liver disease and non-steroidal anti-inflammatory use. Investigations revealed anaemia with haemoglobin of 62 g/L, liver function derangement (Gamma-glutamyl transferase 251 U/L, alanine transaminase 40 U/L, bilirubin 84 umol/L, alkaline phosphatase 85 U/L), coagulopathy (International Normalized Ratio 1.6) and acute kidney injury (Creatinine 285 umol/L). Gastroscopy demonstrated no signs of upper gastrointestinal bleeding or portal hypertension. A large volume haematochezia occurred necessitating resuscitation with massive transfusion protocol, and colonoscopy was abandoned in favour of computerized tomography (CT) angiography, which revealed a large varix feeding the caecum. Urgent laparotomy and a right hemicolectomy was performed with application of abdominal vacuum dressing. The hemicolectomy sample was opened on back table demonstrating large caecal varix causing intraluminal bleeding. The patient was stabilized in intensive care, and a further laparotomy was performed 2 days later where an end ileostomy was formed. Caecal varices have been reported in literature with management via trans-jugular intrahepatic portosystemic shunt, endoscopically or conservatively with beta-blockade. Here we present, to the best of the author’s knowledge, the first reported case of successful surgical management of caecal varices.
Possible circumstellar interaction origin of the early excess emission in thermonuclear supernovae
Authors: Hu Maokai , Wang Lifan , Wang Xiaofeng , Wang Lingzhi
Published: August 2023

Type Ia supernovae (SNe Ia) arise from the thermonuclear explosion in binary systems involving carbon–oxygen white dwarfs (WDs). The pathway of WDs acquiring mass may produce circumstellar material (CSM). Observing SNe Ia within a few hours to a few days after the explosion can provide insight into the nature of CSM relating to the progenitor systems. In this paper, we propose a CSM model to investigate the effect of ejecta−CSM interaction on the early-time multiband light curves of SNe Ia. By varying the mass-loss history of the progenitor system, we apply the ejecta−CSM interaction model to fit the optical and ultraviolet (UV) photometric data of eight SNe Ia with early excess. The photometric data of SNe Ia in our sample can be well matched by our CSM model except for the UV-band light curve of iPTF14atg, indicating its early excess may not be due to the ejecta−CSM interaction. Meanwhile, the CSM interaction can generate synchrotron radiation from relativistic electrons in the shocked gas, making radio observations a distinctive probe of CSM. The radio luminosity based on our models suggests that positive detection of the radio signal is only possible within a few days after the explosion at higher radio frequencies (e.g. ∼250 GHz); at lower frequencies (e.g. ∼1.5 GHz), the detection is difficult. These models lead us to conclude that a multimessenger approach that involves UV, optical, and radio observations of SNe Ia a few days past explosion is needed to address many of the outstanding questions concerning the progenitor systems of SNe Ia.
The evolution of the Milky Way’s thin disc radial metallicity gradient with K2 asteroseismic ages
Authors: Willett Emma , Miglio Andrea , Mackereth J Ted , Chiappini Cristina , Lyttle Alexander J , Elsworth Yvonne , Mosser Benoît , Khan Saniya , Anders Friedrich , Casali Giada , Grisoni Valeria
Published: August 2023

The radial metallicity distribution of the Milky Way’s disc is an important observational constraint for models of the formation and evolution of our Galaxy. It informs our understanding of the chemical enrichment of the Galactic disc and the dynamical processes therein, particularly radial migration. We investigate how the metallicity changes with guiding radius in the thin disc using a sample of red giant stars with robust astrometric, spectroscopic, and asteroseismic parameters. Our sample contains 668 stars with guiding radii 4 < Rg < 11 kpc and asteroseismic ages covering the whole history of the thin disc with precision ${\approx} 25 {{\, \rm per\ cent}}$. We use MCMC analysis to measure the gradient and its intrinsic spread in bins of age and construct a hierarchical Bayesian model to investigate the evolution of these parameters independently of the bins. We find a smooth evolution of the gradient from ≈−0.07 dex kpc−1 in the youngest stars to ≈−0.04 dex kpc−1 in stars older than 10 Gyr, with no break at intermediate ages. Our results are consistent with those based on asteroseismic ages from CoRoT, with that found in Cepheid variables for stars younger than 1 Gyr, and with open clusters for stars younger than 6 Gyr. For older stars we find a significantly lower metallicity in our sample than in the clusters, suggesting a survival bias favouring more metal-rich clusters. We also find that the chemical evolution model of Chiappini '09 is too metal poor in the early stages of disc formation. Our results provide strong new constraints for the growth and enrichment of the thin disc and radial migration, which will facilitate new tests of model conditions and physics.
On the origin of planetary-mass objects in NGC 1333
Authors: Parker Richard J , Alves de Oliveira Catarina
Published: August 2023

The dominant formation mechanism of brown dwarfs and planetary-mass objects (PMOs) in star-forming regions is presently uncertain. Do they form like stars, via the collapse and fragmentation of cores in giant molecular clouds, or do they form like planets in the discs around stars and are ejected via dynamical interactions? In this paper, we quantify the spatial distribution of substellar objects in NGC 1333, in particular focusing on PMOs that have been the target of recent deep imaging observations. We find that these objects have a spatial distribution that is indistinguishable from the stars, and more massive brown dwarfs. We also analyse N-body simulations and find that a population of ejected planets would have a significantly different spatial and kinematic distribution from stars, and brown dwarfs that also formed through gravitational collapse and fragmentation. We therefore conclude that the low-mass substellar objects in NGC 1333 formed more like stars than planets, although we predict that a population of hitherto undetected ejected PMOs may be lurking in this and other star-forming regions.
Challenges faced by nurses engaged in rheumatology care in Japan
Authors: Fusama Mie , Nakahara Hideko , Gregg Misuzu , Kuroe Yuriko , Urata Yukitomo , Kawahata Kimito , Kawahito Yutaka , Kojima Masayo , Sugihara Takahiko , Hashimoto Motomu , Miyamae Takako , Murashima Atsuko , Mori Masaaki , Yajima Nobuyuki , Matsui Toshihiro
Published: August 2023

Objectives

This study aimed to identify the challenges faced by nurses engaged in rheumatology care in Japan.

Methods

We conducted a questionnaire survey of nurses in Japan in 2020 on challenges experienced in rheumatology care. The participants were nurses certified by the Japan Rheumatism Foundation. Participants’ answers were coded and categorized based on relevant phrases and words. Content analysis was performed on the findings.

Results

Responses were collected from 162 participants, and a total of 228 issues were identified. Eighteen categories with 56 subcategories emerged from the data analysis, which were grouped into five types of challenges: (1) communication, (2) understanding, (3) expertise, (4) system, and (5) collaboration. In particular, the results highlighted deficiencies in needs-based multidisciplinary team care.

Conclusion

This study elucidated issues experienced by rheumatology nurses in clinical settings in Japan. Furthermore, this investigation revealed the necessity of patient-centred multidisciplinary team care, including health professionals, patients, and other relevant individuals. This study provided practical directions to facilitate the implementation of effective care focused on improving patients’ quality of life.
BSBM-15 SYSTEMIC AND LOCAL IMMUNE RESPONSES FOLLOWING STEREOTACTIC RADIOSURGERY TO BRAIN METASTASES FROM HER2-AMPLIFIED BREAST CANCER
Authors: Sia Joseph , D'Souza Criselle , Castle Becky , Huang Yu-Kuan , Siva Shankar , Neeson Paul
Published: August 2023

BACKGROUND

Brain metastases (BMs) afflict 30-50% of HER2-amplified breast cancer (HER2-BC) patients. Stereotactic radiosurgery (SRS) is a highly effective focal treatment for BMs. Extracranial radiotherapy can promote anti-tumor immune responses that synergize with immunotherapy, but whether this applies to the brain microenvironment remains unclear. Here, we examined blood and BM samples from HER2-BC patients in the TROG 16.02 translational sub-study for immunological effects of SRS (ACTRN12616001265460).

METHODS

Blood samples from 10 patients taken pre- and 7-14 days post-SRS to intact HER2-BC BMs or post-resection BM cavities were analyzed by mass and flow cytometry for immune cell and cytokine modulation. One patient received pre-operative SRS for a BM that recurred 6 months after resection, followed by re-resection of the BM 7 days post-SRS. Tumors from pre- and post-SRS timepoints in this patient were analyzed by bulk RNAseq and immunohistochemistry.

RESULTS

Monocytes, CD8+ T effector memory and regulatory T cells were enriched in blood post-SRS, while conventional dendritic cells, CD4+ T early and CD4+ TEMRA cells were diminished. Stem cell factor (SCF) concentration, a growth factor important for monocyte production, was elevated in plasma post-SRS. In the tumor, SRS upregulated gene signatures for monocyte/macrophage processes (including SCF gene transcript levels), antigen presentation, and T cell activation. Cell type deconvolution from RNAseq suggested an SRS-induced loss of metastatic tumor cells and enrichment of macrophages and CD4+ T cells. Immunohistochemistry corroborated the influx of CD68+ macrophages and CD3+ T cells into tumor and brain regions post-SRS, with spatial co-localization evident between the cell types. Furthermore, the pre-SRS immune-excluded phenotype in tumor regions was no longer observed post-SRS.

CONCLUSION

Systemic and local immunological changes in this homogenous patient cohort receiving SRS to HER2-BC BMs suggest a radiation-induced adaptive immune response intracranially, involving the monocyte-macrophage lineage as antigen presenting cells, that should be further explored.
BSLD-01 DYNAMIC CONTROL OF CSF FOR PERSONALIZED CNS DRUG DELIVERY FOR LEPTOMINGEAL DISEASE
Authors: Kumthekar Priya , Benatti Hector Ribeiro , Taghian Toloo , Nagpal Seema , Gormley William , Baker William , Patel Rajan , Brown Emma , Glicksman Marcie , Gray-Edwards Heather
Published: August 2023

BACKGROUND

Appropriate drug distribution is needed for effective treatment of brain metastases and leptomeningeal disease. Lack of proper drug bioavailability in the CNS contributes to the poor outcome in these patients. EnClear Therapies has developed a device delivering intrathecal therapeutics utilizing the dynamic control of CSF flow through an external pump. Herein, we look at intrathecal drug delivery of methotrexate with EnClear’s system and its impact of drug concentration in CNS tissue in sheep and non-human primates.

METHODS

EnClear’s system utilizes two implantable catheters (lateral ventricle and lumbar thecal sac) and an extracorporeal pump that controls the speed and direction of CSF flow. Software continuously monitors and reports the output from sensor arrays for pressure, respiration, and heart rate. Imaging studies were used to track the CSF flow characteristics during the use of EnClear’s system. Data from administration of methotrexate followed by the use of EnClear’s system was compared to the current standard of delivery, intracerebroventricular or lumbar intrathecal administration. Methotrexate levels were measured with LC/MS in CSF, blood, and multiple CNS and peripheral tissues.

RESULTS

There was a two-fold increase in methotrexate levels in multiple regions of the brain including deeper brain structures including the striatum using EnClear's system, compared to traditional lumbar intrathecal and intracerebroventricular delivery. Higher peak levels of methotrexate were reached in the CSF with the use of EnClear’s system, with simultaneous reduction in the peripheral nerves and systemic tissues – a potential source of toxicity.

CONCLUSIONS

In large animal studies, EnClear’s system has for the first time, demonstrated increased brain parenchymal drug levels via intrathecal delivery. Drug delivery with this novel device has shown improved distribution throughout the CNS and leptomeninges as compared to traditional intrathecal drug delivery and decreased peripheral distribution.
BSLD-02 ELUCIDATING LEPTOMENINGEAL MICROENVIRONMENT CUES THAT PROMOTE METASTASIS AND CHEMOTHERAPY RESISTANCE IN HIGH-RISK MEDULLOBLASTOMA
Authors: Reinecke James , Garcia Leyre Jimenez , Roberts Ryan
Published: August 2023

Medulloblastoma is a molecularly heterogenous brain tumor of the cerebellum and is a leading cause of pediatric cancer mortality due to its propensity for leptomeningeal metastasis. Leptomeningeal metastasis occurs in over 20-30% of patients despite age- and risk- adapted chemoradiation therapy. The mechanisms responsible for medulloblastoma metastasis and therapy resistance remain incompletely understood. The leptomeninges represent a fundamentally distinct microenvironment from the primary cerebellar tumor. We hypothesized that unique signaling inputs from the cellular and extracellular milieu of the leptomeninges drive distinct medulloblastoma biology that leads to resistance to current standard of care therapy. We tested this hypothesis using Group 3-MYC amplified (Grp3-MA) cell lines given their high metastatic potential. Primary tumors grow within a glycosaminoglycan (hyaluronan) rich matrix while leptomeningeal metastases grow in a laminar fashion attached to leptomeningeal (pial) cells that were enriched for laminins, collagens, and fibronectin. Analogously, Grp3-MA cells grow in suspension at steady state, but subpopulations readily adhere to a leptomeningeal membrane mimetic in vitro. This attachment required integrin beta 1 (ITGB1) and promoted chemotherapy resistance. We additionally have created a novel co-culture model wherein medulloblastoma cells grow as adherent clusters on a layer of primary leptomeningeal cells in an ITGB1 dependent manner. We are using this co-culture platform to perform single cell RNA sequencing and ligand receptor analysis to understand how cell-cell communication between leptomeningeal cells and medulloblastoma cells promotes tumor cell growth. Collectively, our studies demonstrate that cues from the leptomeningeal microenvironment alter medulloblastoma cell behavior and are attractive targets for developing novel therapies against metastasis.
CLRM-01 DETERMINANTS OF SYMPTOMATIC INTRACRANIAL PROGRESSION FOLLOWING AN INITIAL STEREOTACTIC RADIOSURGERY COURSE
Authors: Leng Jim , Huang Christina , Qazi Jamiluddin , Carpenter David , Arshad Muzamil , Schultz Olivia , Mullikin Trey , Reitman Zachary , Kirkpatrick John , Floyd Scott , Fecci Peter , Chmura Steven , Hong Julian , Salama Joseph
Published: August 2023

To determine the prognostic significance of neurologic symptoms at progression for patients with brain metastases (BM) undergoing stereotactic radiosurgery (SRS), all patients completing an initial course of SRS between 1/2015 and 12/2020 were identified across two institutions. Intracranial progression (ICP) was recorded, with symptomatic ICP (SICP) defined as new/worsening neurologic symptoms without another etiology. Overall survival (OS), freedom from ICP (FFICP), and freedom from symptomatic ICP (FFSICP) were assessed via Kaplan-Meier method. For FFSICP, patients were censored at time of death or asymptomatic ICP. Logistic regression models tested parameter association to neurologic symptoms. Cox proportional hazard models tested parameters impacting FFICP and FFSICP. Among 1383 patients, median age was 63.4 years, 54.8% were female, and 45.6% had KPS ≥90. Common primary sites were non-small cell lung (48.7%), breast (14.7%), and melanoma (8.5%). 46.9% had oligometastatic disease (≤5 foci), and 53.4% had >1 BM. 26.1% patients had prior surgical resection, and 10.3% had WBRT. With a median follow up of 8.7 months, 504 (36%) and 194 (14%) experienced asymptomatic and symptomatic ICP respectively. OS was worse for patients experiencing SICP (median 10.2 vs 17.9 months, p<0.001). Among patients with ICP, SICP was associated with total treated tumor volume (per-ml, OR 1.01, 95% CI 1.00-1.02), while those with more recent MRI imaging and post-SRS systemic therapy was associated with asymptomatic ICP. Patients who received post-SRS chemotherapy (HR 0.64, 95% CI 0.45-0.90), immunotherapy (HR 0.49, 95% CI 0.34-0.71), or targeted therapy (HR 0.49, 95% CI 0.33-0.73) had better FFSCIP. Worse FFSCIP was associated with melanoma (HR 2.56, 95% CI 1.49-4.38), and greater than 2 BMs (HR 2.24, 95% CI 1.56-3.22). SICP is prognostic for OS, and is associated with melanoma, no systemic therapy post-SRS, and greater number of BMs. These data further support the use of SICP as a meaningful clinical endpoint.
CLRM-02 CALCIFIED SPINAL MENINGIOMAS: A SYSTEMATIC REVIEW OF CLINICAL CHARACTERISTICS, TREATMENT STRATEGIES, AND OUTCOMES
Authors: Reddy Raghuram , Shah Darsh , Palmisciano Paolo
Published: August 2023

Calcified meningiomas involving the spine are rare but can pose significant surgical challenges. We systematically reviewed the literature on calcified spinal meningiomas. PubMed, EMBASE, Web-of-Science, and Scopus databases were searched to include studies reporting clinical data of patients with calcified spinal meningioma. Included articles were analyzed for symptoms, imaging, spine level of the tumor, tumor location relative to the spinal cord, calcification status, treatment regimen, recurrence, progression-free survival, and outcomes. A total of 35 articles encompassing 94 patients were included. Most patients were female (90.4%), presenting with lower extremity weakness (44%) and/or lower extremity paresthesia (38.1%). Most calcified spinal meningiomas occurred in the thoracic spine (82%) and on the dorsal (33.3%) or ventral (27.2%) side relative to the spinal cord. Most tumors were intradural (87.2%). Histologically, most calcified spinal meningiomas were WHO grade I (97.4%) and psammomatous (50.7%). Most tumors demonstrated macroscopic calcification (48.9%). Most patients underwent gross total resection (91.5%) through a posterior approach (100%). Two patients (2.1%) received adjunctive radiotherapy. The most common treatment related complication was CSF leakage. Post-operatively, most patients demonstrated symptomatic improvement (75.5%) and 2 (2.1%) had local tumor recurrence. Calcified spinal meningiomas are uncommon but benign entities. These neoplasms tend to adhere to surrounding tissues and nerves and, thus, can be surgically challenging to remove. In most patients, safe gross total resection remains the standard of care, but accurate surgical planning is necessary to reduce the risks of postoperative complications.
NEIM-03 A GRADUAL INTEGRATION MODEL BASED ON MRI TO PREDICT MOLECULAR PROFILES IN PATIENTS WITH GLIOMA
Authors: Chen Hongyu , Miao Xuan , Tang Ming , Chen Zhongping , Chen Yinsheng
Published: August 2023

Glioma is the most common primary brain tumor. Molecular profiles, including IDH mutation, 1p/19q co-deletion, and MGMT promoter methylation, are highly correlated with the prognosis and clinical decision-making of glioma. To predict the molecular profiles from rough segmentation MRI, we developed and validated a gradual integration model. We proposed a multi-task pseudo-3D model based on rough segmented multiparametric MRI to predict molecular profiles. In this model, convolution along the depth axis was performed between convolution blocks. A total of 750 patients with glioma were retrospectively enrolled from Sun Yatsen University Cancer Center(n=576) and The Cancer Imaging Archive(n=167) to validate the performance of the framework. The model was developed and validated on the local dataset and tested on an independent external (TCIA) test set. For IDH, 1p/19q, and MGMT predictions on the TCIA set, the gradual fusion model achieves AUCs of 0.87, 0.80, and 0.71, respectively, outperforming both input or output integration models and 2D models. To conclude, our gradual fusion model demonstrated the potential to predict molecular profiles based on pre-treatment MRI. Gradual integration may be a reliable method to design 3D medical imaging models.
SDPS-36 CLINICAL PRESENTATION IS A USEFUL PROGNOSTIC MARKER IN PATIENTS WITH BRAIN METASTASES
Authors: Cacho-Díaz Bernardo , Arrieta Oscar , Gonzalez-Gonzalez Ethan
Published: August 2023

BACKGROUND

Brain metastases are the most common malignant intracranial tumors and a leading cause of cancer-associated death. The influence on survival of their clinical presentation is scarce.

AIM

To determine if the clinical presentation of patients with brain metastases is associated with survival.

METHODS

A retrospective database of patients with brain metastases seen at a single center from 2010 to 2022 was analyzed. Clinical presentation and its association with survival were measured individually and adjusted for other prognostic variables.

RESULTS

From 822 patients, the most common symptoms were headache 53%, focal weakness 35%, visual disorders 24%, nausea/vomiting 23%, seizures 22%, and altered mental status 18%. Clinical presentations associated with survival after multivariate analysis were no symptoms [HR 0.55 (95%CI 0.39-0.79), P = 0.001], focal weakness [HR 1.21 (95%CI 1.01-1.44), P = 0.032], altered mental status [HR 1.24 (95%CI 1.01 – 1.52), P = 0.038], and visual disorders [HR 1.29 (95%CI 1.07-1.46), P = 0.007. Adding the clinical information to the graduated prognostic score improved its prognostic performance measured by both the C-statistic and the Akaike information criteria.

CONCLUSION

Clinical symptoms should be considered in all patients with brain metastases for they are associated with outcomes.
SDPS-41 PATHOMICS AUGMENTS PREDICTIVE SURVIVAL MODELLINGIN MEDULLOBLASTOMA
Authors: Mahtabfar Aria , Familiar Ariana , Kazerooni Anahita Fathi , Kiani Mahsa , Haldar Debanjan , Viswanathan Karthik , Resnick Adam , Storm Phillip , Viaene Angela , Nabavizadeh Ali
Published: August 2023

PURPOSE

Medulloblastoma survival and treatment response has shown wide variability based on molecular and genomic subtyping. Early prediction of overall survival (OS) may afford clinicians an opportunity to develop individualized treatment paradigms for patients. Computational pathology (“pathomics”) confers the ability to extract sub-visual histopathologic features using high-throughput analysis to better characterize tumor biology or behavior.

METHODS

Using the Children’s Brain Tumor Network database, pediatric patients with available clinical data and whole-slide images (WSI) were evaluated for inclusion in the study. 1mm x 1mm regions-of-interest (ROI) on each H&E-stained WSI were selected to identify tumor-rich areas for subsequent pathomic analysis, and 49 quantitative pathomics features were extracted using a digital pathology software package (Qupath). LASSO cox proportional hazard model with stratified 5-fold cross-validation was used to identify high-performing features and generate risk scores. Estimated risk scores were subsequently used to stratify patients into low-, medium- and high-risk OS cohorts. Two separate models were trained including either: 1) clinical variables only; or 2) combined clinical and pathomic features.

RESULTS

A total of 84 patients with median age at diagnosis of 8.61 years (range 0.31-21.72), and median OS of 45.6 months (range 0.76-195.87)) were included in the study. A survival model built using only clinical features yielded a concordance index (c-index) of 0.76 compared to actual outcomes (stratification: p<0.001). Combining clinical and high-performing pathomic features, however, yielded the best performance of the model, showing disparate outcomes between low-, medium- and high-risk groups (p<0.001) with resultant c-index of 0.85.

CONCLUSION

Our results highlight the utility of pathomics analysis in predicting survival in patients with pediatric medulloblastoma, which can be used to guide treatment strategy. Further work will aim to perform our analysis on an unseen validation set to improve its performance and applicability in the clinical realm.
SPCR-11 DEMOGRAPHIC DISPARITIES AND PROGNOSTIC FACTORS IN PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA: A SEER DATABASE ANALYSIS
Authors: Ramesh Nithya , Baralo Bohdan , Chitra Shanjeev Kumar Rajeshkumar , Naik Mansi , Chhibber Sherley , Thirumaran Rajesh
Published: August 2023

Accounting for 3-4% of all central nervous system malignancies, primary CNS lymphoma (PCNSL) is a rare but aggressive form of extranodal non-Hodgkin lymphoma. Although recent studies have demonstrated an overall decline in the incidence, certain demographics are known to be more affected than others. We reviewed the queried Surveillance, Epidemiology, and End Results (SEER) database, 17 registries, Nov 2021 sub (2000-2019) for lymphoid neoplasm recode 2021 revision with primary site codes C69.1-69.4, C69.9-70.1, C70.9-72.5, C72.8-72.9. Patients of unknown race, ethnicity, and stage of the disease were excluded. We used Cox proportional hazard regression to assess the determinants of overall survival (OS) and cause-specific survival (CSS). Significance level was set to 0.05. Our search included 5910 patients. The mean age at diagnosis was 61.8 ± 15.8 years. Males accounted for 53.67% of the patients. Racial demographics showed a predominance of Whites (66.1%), followed by Hispanics (15.6%), Asian/pacific islanders (10.3%), Blacks (7.4%), and American Indians/Alaska Natives (0.45%). Most common histology was diffuse large B-cell lymphoma (67.74%). Most patients were diagnosed at stage I (76.5%), followed by stage IV (19.7%) of the disease. Older patients had worse OS (HR 1.03 [1.027;1.032]) and CSS (HR 1.021 [1.018;1.024]). Females had better OS 0.853 [0.803;0.9059]) and CSS (HR 0.8871 [0.8145;0.966]) compared to males. Indolent (follicular and marginal zone) lymphomas were associated with better OS (HR 0.3169 [0.2647-0.3759]) and CSS (HR 0.4265 [0.3494-0.5152]) compared to large B-cell lymphoma. Black patients had worse OS (1.608 [1.421-1.813]) and CSS (HR 1.385 [1.165-1.635]). While Hispanic ethnicity did not influence OS, it was associated with worse CSS (1.158 [1.025;1.304]). Stage at diagnosis did not have a statistically significant association with survival. These results suggest a need for additional research targeting high-risk demographics to develop tailored treatments, enhance care accessibility, and address possible inequities in the management of PCNSL.
SYST-23 CDK1 AS AN INDEPENDENT PROGNOSTIC INDICATOR AND POTENTIAL THERAPEUTIC TARGET IN GLIOMA
Authors: Wang Yu , Zhou Huandi , Han Xuetao , Zhang Dongdong , Hou Liubing , Xue Xiaoying , Li Yuehong
Published: August 2023

Glioma is the most common primary malignant tumor in the brain with extremely poor prognosis. Firstly, in order to find the important genes and mechanisms involved in the initiation and progression of glioma, we selected four groups of gene expression profiles from GEO dataset include GSE29796, GSE4290, GSE50161 and GSE7696 for comprehensive data analysis. We identified 360 differentially expressed genes (DEGs), then we screened out core gene which is CDK1 by protein-protein interaction (PPI) network analysis. So as to clarify whether CDK1 is an independent prognostic factor for glioma, we performed expression analysis and prognostic analysis. Meanwhile, in order to verify the expression and survival of CDK1, we used Western blot to detect CDK1 expression of 15 glioma specimens and corresponding adjacent tissues. Moreover, we divided the expression values of CDK1 gene in the CGGA database into high and low groups based on the median for differential expression analysis. Finally, to explore the molecular mechanism of action of CDK1 in gliomas, we conducted gene ontology (GO) enrichment analysis and gene collection enrichment analysis (GSEA),and performed gene co-expression analysis. The results revealed that the expression level of CDK1 in glioma was significantly higher than normal tissues, its high expression was closely associated with poor survival of glioma. And the prognostic analysis showed that CDK1 was an independent prognostic index of glioma. Through the mechanism analysis of GO and GSEA, it is demonstrated that CDK1 plays an important role in the mitosis cell cycle of glioma, and inhibiting the expression of CDK1 can affect the proliferation of glioma cells. Coexpression analysis displayed that the high expression of PCNA, MCM2, MCM3, MCM4, MCM6, PLK1, TTK and MAD2L1 are also correlated to the poor survival and prognosis of glioma. Hence CDK1 is an independent prognostic factor and potential therapeutic target of glioma. Furthermore ,we can affect the proliferation of glioma cells through inhibiting the expression of CDK1.
TIPS-19 TRIAL IN PROGRESS: SECONDARY BRAIN METASTASES PREVENTION AFTER ISOLATED INTRACRANIAL PROGRESSION ON TRASTUZUMAB/PERTUZUMAB OR T-DM1 IN PATIENTS WITH ADVANCED HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2+ BREAST CANCER WITH THE ADDITION OF TUCATINIB (BRIDGET)
Authors: Van Swearingen Amanda , Sammons Sarah , Noteware Laura , Bagegni Nusayba , Moulton Kelly , Threatt Stevie , Jaggers Denise , Shea Shannon , Lipp Eric , Riley Erin , Jung Sin-Ho , Broadwater Gloria , Ross Masey , Strickland Kimberly , Beyer Sasha , Conlin Alison , Morikawa Aki , Murthy Rashmi , Anders Carey
Published: August 2023

Despite trastuzumab-based therapy, up to half of patients with HER2+ metastatic breast cancer (MBC) will develop brain metastases (BrM). First-line therapy for HER2+ MBC, taxane/trastuzumab/pertuzumab (TP), demonstrates poor brain permeability. Isolated brain relapse with stable/absent extracranial disease remains a clinical problem in both the adjuvant and metastatic settings, and current guidelines recommend continuing current systemic therapy following local therapy. Tucatinib, a brain-penetrable HER2-inhibitor, when added to trastuzumab and capecitabine improves intracranial PFS and OS in patients with stable/active HER2+ BrMs. We hypothesize that adding tucatinib to TP or T-DM1 in patients with HER2+ MBC with isolated brain relapse or progression could delay or prevent the development of further intracranial lesions and improve OS. BRIDGET (NCT05323955) is a single arm, phase II study of tucatinib added to TP or T-DM1 after local therapy in patients with isolated brain relapse or progression. A total of 48 patients at 9 U.S. sites through HCRN with HER2+ MBC will be enrolled after 1st or 2nd BrM relapse/progression within 8 weeks of local therapy. Patients must currently be receiving TP or T-DM1 in the metastatic setting, or adjuvant trastuzumab-based or T-DM1 therapy with isolated brain recurrence. Extracranial disease must be stable per RECISTv1.1 or absent. Patients will receive tucatinib added to their current therapy. The primary objective is intracranial PFS compared to a historical control (H0: historical iPFS <5 months (mos), HA: iPFS >8 mos) of the HER2CLIMB trial. In these patients, median time from brain progression to second progression/death was 7.6 mos with tucatinib versus 3.1 mos in the control arm. Secondary endpoints include PFS by RECISTv1.1, PFS of extracranial disease, locally treated versus new distant intracranial metastasis PFS, site of first progression, OS, and toxicity. Collection of correlative specimens and patient-reported outcomes (FACT-BR, FACIT-Fatigue) are also included.
Symbolic incentives and the recruitment of volunteers for citizen science projects
Authors: Cicognani Simona , Stein Sebastian , Tonin Mirco , Vlassopoulos Michael
Published: August 2023

The provision of activities with external benefits that rely on voluntary contributions may often fall below societal needs. In this article, we focus on such contributions to a citizen science project (the World Community Grid) in which members of the general public are asked to offer unused computer power to advance cutting-edge scientific research. We investigate the role played by symbolic awards in stimulating existing contributors to recruit new contributors for this project. The recruitment campaign we study introduces badges for referrals (visible on each user’s public profile page) varying, across randomized treatment groups, the threshold of successful referrals needed to receive these badges. We find that these symbolic incentives are effective in boosting referrals, and more so when the minimum threshold for achieving symbolic awards is higher. However, the overall effect of the incentives is quite modest, highlighting the challenges of running referral campaigns for the recruitment of volunteers.
Increased Incidence and Risk of Septicemia and Urinary Tract Infection After Clostridioides difficile Infection
Authors: Olsen Margaret A , Keller Matthew R , Stwalley Dustin , Yu Holly , Dubberke Erik R
Published: August 2023

Background

Although increased occurrence of septicemia in persons with Clostridioides difficile infection (CDI) has been reported, incidence rates and risk of septicemia and urinary tract infection (UTI) after CDI are unclear.

Methods

The first episode of CDI was identified using 2011–2017 MarketScan and CMS Medicare data and CDI cases categorized by standard surveillance definitions. Uninfected persons were frequency matched 4:1 to cases by the CDI case surveillance definition. Multivariable Cox proportional hazards models were used to identify risk factors for septicemia and UTI within 90 days of CDI onset, accounting for the competing risk of death in the Medicare population.

Results

The incidence of septicemia was highest after hospital-onset CDI in the Medicare, younger commercial, and younger Medicaid populations (25.5%, 15.7%, and 19.5%, respectively) and lowest in those with community-associated CDI (3.8%, 4.3%, and 8.3%, respectively). In contrast, the incidence of UTI was highest in those with other healthcare facility onset CDI in all 3 populations (32.1%, 24.2%, and 18.1%, respectively). Hospital-onset CDI was associated with highest risk of septicemia compared with uninfected controls in all 3 populations. In the younger populations, risk of septicemia was more uniform across the CDI surveillance definitions. The risk of UTI was significantly higher in all CDI surveillance categories compared to uninfected controls, and among CDI cases it was lowest in those with community-associated CDI.

Conclusions

The incidence of septicemia is high after CDI, particularly after hospital-onset infection. Additional preventive measures are needed to reduce infectious complications of CDI.
Genomic variations combined with epigenetic modifications rewire open chromatin in rice
Authors: Li Mengqi , Feng Yilong , Han Qi , Yang Ying , Shi Yining , Zheng Dongyang , Zhang Wenli
Published: August 2023

Cis-regulatory elements (CREs) fine-tune gene transcription in eukaryotes. CREs with sequence variations play vital roles in driving plant or crop domestication. However, how global sequence and structural variations (SVs) are responsible for multilevel changes between indica and japonica rice (Oryza sativa) is still not fully elucidated. To address this, we conducted multiomic studies using MNase hypersensitivity sequencing (MH-seq) in combination with RNA sequencing (RNA-seq), chromatin immunoprecipitation sequencing (ChIP-seq), and bisulfite sequencing (BS-seq) between the japonica rice variety Nipponbare (NIP) and indica rice variety 93-11. We found that differential MNase hypersensitive sites (MHSs) exhibited some distinct intrinsic genomic sequence features between NIP and 93-11. Notably, through MHS–genome-wide association studies (GWAS) integration, we found that key sequence variations may be associated with differences of agronomic traits between NIP and 93-11, which is partly achieved by MHSs harboring CREs. In addition, SV-derived differential MHSs caused by transposable element (TE) insertion, especially by noncommon TEs among rice varieties, were associated with genes with distinct functions, indicating that TE-driven gene neo- or subfunctionalization is mediated by changes of chromatin openness. This study thus provides insights into how sequence and genomic SVs control agronomic traits of NIP and 93-11; it also provides genome-editing targets for molecular breeding aiming at improving favorable agronomic properties.
Evaluation of a therapist-guided virtual psychological pain management program when provided as routine care: a prospective pragmatic cohort study
Authors: Dear Blake F , Walker Jennie , Karin Eyal , Asrianti Lia , England Jonathan , Feliciano Ivy , Bisby Madelyne A , Nielssen Olav , Kayrouz Rony , Cross Shane , Staples Lauren G , Hadjistavropoulos Heather D , Titov Nickolai
Published: August 2023

Introduction

Numerous randomized controlled trials have evaluated the outcomes of internet-delivered psychological pain management programs (PMPs) as a way of increasing access to care for people with chronic pain. However, there are few reports of the effectiveness of these PMPs when provided as part of routine care.

Methods

The present study sought to report the clinical and demographic characteristics of users (n = 1367) and examine the effectiveness of an established internet-delivered psychological PMP program in improving several pain-related outcomes, when offered at a national digital mental health service over a 5-year period. It also sought to comprehensively explore predictors of treatment commencement, treatment completion, and clinical improvement.

Results

Evidence of clinical improvements (% improvement; Hedges g) were found for all outcomes, including pain interference (18.9%; 0.55), depression (26.1%; 0.50), anxiety (23.9%; 0.39), pain intensity (12.8%; 0.41), pain self-efficacy (-23.8%; -0.46) and pain-catastrophizing (26.3%; 0.56). A small proportion of users enrolled but did not commence treatment (13%), however high levels of treatment completion (whole treatment = 63%; majority of the treatment = 75%) and satisfaction (very satisfied = 45%; satisfied = 37%) were observed among those who commenced treatment. There were a number of demographic and clinical factors associated with commencement, completion and improvement, but no decisive or dominant predictors were observed.

Discussion

These findings highlight the effectiveness and acceptability of internet-delivered psychological PMPs in routine care and point to the need to consider how best to integrate these interventions into the pathways of care for people with chronic pain.