bluuebunny/crossref_metadata_2025_split huggingface dataset:
54. tGLI1 IS AN ACTIONABLE THERAPEUTIC TARGET IN BREAST CANCER BRAIN METASTASES
Authors: Doheny Daniel , Sirkisoon Sherona , Rimkus Tadas , Zhu Dongqin , Aguayo Noah , Anguelov Marlyn , Manore Sara , Regua Angelina , Thomas Alexandra , Henson-Masters Adrianna , Strowd Roy , Lo Hui-Wen 
Published: August 2020

Abstract
Breast cancer is the second leading cause of brain metastases in women; patients with breast cancer brain metastasis (BCBM) survive an average of 6–18 months following diagnosis. Cancer stem cells are thought to be one of the driving forces behind distant metastasis, treatment resistance, and late-stage recurrence. The hedgehog-smoothened pathway has been identified as an important mediator of breast cancer stem cells (BCSC); however, FDA-approved therapies targeting smoothened have demonstrated limited clinical efficacy in breast cancer. Despite advances made in understanding BCSC, it is still challenging to effectively target BCSC underscoring the need to identify and inhibit novel mediators of BCSC for treating BCBM patients. Our laboratory recently reported that truncated glioma-associated oncogene homolog 1 (tGLI1) promotes preferential metastasis to the brain in breast cancer by activating BCSC and astrocytes in the tumor microenvironment (Oncogene 39:64–78, 2020). tGLI1 was discovered in our laboratory as an alternatively spliced GLI1 that functions as a tumor-specific gain-of-function transcription factor and terminal effector of the hedgehog pathway. We found that tGLI1 knockdown abrogated BCBM, providing the rationale to therapeutically target tGLI1. Cell-based chemical screens followed by validations demonstrated that ketoconazole, an FDA-approved azole antifungal, specifically inhibits tGLI1 leading to suppression of BCSC in vitro and BCBM in vivo. Based on these data, we opened a window-of-opportunity study in patients with BCBM to determine if ketoconazole penetrates the blood-brain barrier (BBB) and alters tGLI1 signaling in humans (NCT03796273). Preliminary sample analysis has confirmed tGLI1 expression in collected BCBM samples. To help identify more effective tGLI1 inhibitors, we screened 63 azole compounds for tGLI1-selectivity and identified four additional compounds as potential tGLI1 inhibitors. Animal studies were performed to compare the efficacy of these four compounds with ketoconazole in suppressing BCBM. Collectively, these data establish tGLI1 as an actionable target for BCBM.
56. TUMOR-HOMING STEM CELL THERAPY INHIBITS THE PROGRESSION OF BREAST CANCER LEPTOMENINGEAL CARCINOMATOSIS
Authors: Jiang Wulin , Valdivia Alain , Mercer-Smith Alison , Anders Carey , Hingtgen Shawn 
Published: August 2020

Abstract

INTRODUCTION
Leptomeningeal carcinomatosis remains one of the most lethal forms of central nervous system metastasis, with a median survival of only 4 months. Effective new therapies are urgently needed to treat this highly aggressive cancer. In this study, we used models of both prophylactic and established leptomeningeal disease to investigate the efficacy of engineered tumor-homing neural stem cells (NSCs) therapy for breast cancer leptomeningeal carcinomatosis.

METHODS
Personalized NSC carriers were created using Sox2 overexpression to transdifferentiate human fibroblasts into induced NSCs (iNSCs) that home to cancer cells and carry therapeutic agents to induce tumor kill. Leptomeningeal models were created by engineering MDA-MB231-Br human breast cancer cells with fluorescent and bioluminescent reporters, then using intracisternal injection to inoculate Nude mice with the tumor cells. iNSC therapy was evaluated by infusing iNSCs releasing the pro-apoptotic agent TRAIL into the lateral ventricle of mice either 1 week prior to or 3 days after tumor inoculation for prophylactic or established tumor treatment respectively. Tumor progression in the brain and spinal cord was monitored by serial bioluminescence imaging (BLI).

RESULTS
Serial BLI showed that intracerebroventricular (ICV) iNSC-TRAIL therapy reduced the volume of metastatic tumor burden 99.49% in the brain and 99.80% in the spine within 2 weeks post-infusion and extended survival from 24 to 42 days. Additionally, prophylactic iNSC-TRAIL therapy delivered ICV markedly delayed tumor development, with tumors in the brain remaining &gt;1000-fold smaller than control through 1-month post-treatment, below the limit of detection in the spinal cord through 1 month, and eliminating mortality through 50 days post-therapy.

CONCLUSION
These data suggest that iNSC therapy could be a promising treatment option for breast cancer patients with leptomeningeal carcinomatosis.
66. CLINICAL CHARACTERISTICS AND RESULTS OF PEDIATRIC SOLID TUMORS WITH BRAIN METASTASES: EXPERIENCE FROM A SINGLE REFERRAL CANCER CENTER
Authors: Aguilar Clarissa , Toro Víctor , Medina Rina 
Published: August 2020

Abstract

BACKGROUND
80% of childhood cancer are located in low- and middle-income countries (LMIC). The most common form of presentation is disseminated or metastatic disease. The rate of survival has not been equitable across the world, since in these countries only 1 of 5 children are cured.

OBJECTIVE
To evaluate the clinical and histopathological features of patients with metastatic pediatric solid tumors, in a single referral cancer center in Honduras.

METHODS
We conducted a retrospective review of patients diagnosed with pediatric solid tumors from January 2010 to April 2020. Among the 260 patients through a collection form, we obtained: sociodemographic characteristics, clinical presentation at diagnosis, common histological subtypes, sites of metastasis, treatment and outcome at the time of follow-up.

RESULTS
During the last 10 years, 260 cases of childhood cancer were referred to our center for treatment. 127 patients (48.8%), have a solid tumor, patients ranged in age from 1 to 18 years and distribution for sex were 38% for males and 62% females. At the time of initial diagnosis 40/127 (31%) have advanced disease (stages III and IV). We found brain metastases in 22/40 cases (55%), the primary cancer was localized at CNS in 13/22 (59%) and the most common extracranial tumors causing brain metastases were neuroblastoma (4/22), rhabdomyosarcoma (3/22), retinoblastoma (2/22). Currently in the follow-up there were 18/22 (82%) died and 4/22 (18%) are in treatment with palliative intent.

CONCLUSION
There is a lack of information about the epidemiology of brain metastases among children with solid tumors in the low/middle income countries (LMIC) where the prognosis of metastatic disease is very poor, despite efforts, multimodal therapy and multidisciplinary management, in absence of other options like bone marrow transplantation, and reliable access to high-quality medicines. For our countries, timely diagnosis is still the main determining factor for cure.
74. EFFICACY OF HER2-TARGETED THERAPY IN HER2-POSITIVE BREAST CANCER BRAIN METASTASES: A NATIONAL ANALYSIS
Authors: Hulsbergen Alexander , Broekman Marike , Smith Timothy , Iorgulescu Bryan 
Published: August 2020

Abstract

BACKGROUND
Breast cancer brain metastases (BCBM) commonly develop in human epidermal growth factor 2-positive (HER2+) breast cancer, but BCBM patients are underrepresented in clinical trials, leading to a lack of knowledge on the efficacy of HER2-targeted therapy in this population.

METHODS
We analyzed clinical characteristics and outcomes of HER2+ BCBM patients from the National Cancer Database 2010–2016, comprising 70% of newly-diagnosed cancers in the U.S, to assess overall survival (OS) associated with HER2-targeted monoclonal antibody therapy (HER2-mab; i.e. trastuzumab, pertuzumab, and trastuzumab emtansine; encoded as of 2013). Survival was estimated with Kaplan-Meier techniques and compared with landmark analysis and Cox regression. The landmark timepoint was selected at which 75% of HER2-mab patients received HER2-mab, which was within 58 days of diagnosis.

RESULTS
1,059 HER2+ BCBM patients were identified, 717 (67.7%) patients were estrogen receptor negative (ER-) and 342 (32.3%) were ER+. Median follow-up was 12.0 months, at the end of which 73.8% of patients were deceased. Median OS was 12.2 and 22.1 months for ER- and ER+ patients, respectively. HER2-mab usage for BCBM patients rose from 53.6% in 2013 to 71.7% in 2016. 420 BCBM patients had complete data for landmark analyses: 70.0% (n=294) received HER2-mab and 30.0% (n=126) did not, in which HER2-mab was associated with significantly improved OS in both ER- (median 22.2 months, 95%CI: 18.2–25.4; vs. 9.5 mos, 95%CI: 6.3–10.7; p=0.0001) and ER+ (median 25.7 months, 95%CI: 21.4-not reached; vs. 19.6 months, 95%CI: 11.1–35.2; p=0.02) patients. In multivariable Cox landmark analysis adjusted for ER status, age at diagnosis, extracranial disease, chemotherapy, radiotherapy, and metastasectomy; HER2-mab demonstrated significantly improved OS (hazard ratio 0.59 vs. no HER2-mab, 95%CI: 0.44–0.77; p&lt;0.001).

CONCLUSIONS
In this large, national study, HER2-mab was associated with substantially improved overall survival in BCBM patients.
Effects of dietary macronutrients and body composition on glucose homeostasis in mice
Authors: Hu Sumei , Togo Jacques , Wang Lu , Wu Yingga , Yang Dengbao , Xu Yanchao , Li Li , Li Baoguo , Li Min , Li Jianbo , Wang Guanlin , Zhang Xueying , Niu Chaoqun , Mazidi Mohsen , Douglas Alex , Speakman John R 
Published: August 2020

Abstract
As a major health issue, obesity is linked with elevated risk of type 2 diabetes. However, whether disrupted glucose homeostasis is due to altered body composition alone, or whether dietary macronutrients play an additional role, independent of their impact on body composition, remains unclear. We investigated the associations between macronutrients, body composition, blood hormones and glucose homeostasis. We fed C57BL/6N mice 29 different diets with variable macronutrients for 12 weeks. After 10 weeks, intraperitoneal glucose tolerance tests were performed. Generalized linear models were generated to evaluate the impacts of macronutrients, body composition and blood hormones on glucose homeostasis. The area under the glucose curve (AUC) was strongly associated with body fat mass, but not dietary macronutrients. AUC was significantly associated with fasting insulin levels. Six genes from transcriptomic analysis of epididymal white adipose tissue and subcutaneous white adipose tissue were significantly associated with AUC. These genes may encode secreted proteins that play important previously unanticipated roles in glucose homeostasis.
Race and Violence
Authors: Aldama Arturo , Malaver Laura , O'Neal Shawn , Portillos Alejandra Benita 
Published: August 2020

White-supremacist violence; theft of land and resources; the genocide of indigenous peoples and the horrors of violence of stolen and enslaved human beings to build wealth for their colonial overlords, countries, and empires in the United States, the Caribbean, and the Americas; and xenophobic and racialized exploitations of labor produced by people of color are core aspects of US history. The issues, spectacles, histories, and lived experiences of race, racism, and racial, gender, and sexual violence drive the structural oppression of nonwhite communities in the United States and have unique trajectories while also developing unevenly and relationally within shared histories of racial, gender, and sexual violence and economic exploitation. Violence toward people of color started with first contact between European colonizing forces and indigenous communities in the late 15th century. From the late 15th century to the 21st century, the spectacles of lynching; vigilantism; Jim Crow / Juan Crow segregation practices; the imposition of boarding schools and the documented physical, psychological, and sexual violence inflicted on indigenous children; and the extreme anti-Chinese violence of vigilante race riots and xenophobic immigration laws are all legacies continuing into the 2020s. In the 20th century, a range of organized systems and acts of violence continued and emerged, from white-supremacist and patriarchal authority on communities of color; race riots; lynching; massacres; and unlawful imprisonments to the 1943 zoot suit riots, deportation, other acts of state-driven violence, and the rise of mass incarceration. Acts of domestic terrorism by white-supremacist individuals who see Latinx, Muslims, Jews, and other non-Anglo-Saxon communities as threats and invaders to the US body politic are a central feature of the 21st century. Along with vigilante violence toward communities of color, police brutality and deadly force with impunity continue to traumatize communities of color and foments the racial biopower politics of the 21st century, not to mention the ongoing crisis of domestic and gender-driven violence. This article summarizes a range of sources that speak both to empire- and state-driven and vigilante violence in different time frames toward varying communities in the United States and beyond.
Ernest Chausson
Authors: Hart Brian 
Published: August 2020

Amédée-Ernest Chausson (b. 1855–d. 1899) was born in Paris to a wealthy contractor and his wife. Although he obtained a law degree in 1876, music was his true passion. He entered the Paris Conservatoire, where he studied briefly with Jules Massenet and then with César Franck. Between 1879 and 1883 he made several journeys to Bayreuth and became an ardent Wagnerian. He served as secretary of the Société Nationale de Musique from 1886 until his death. Chausson and his wife, Jeanne, maintained an active salon that drew many prominent figures from all the arts, and he developed close relationships with many of them, most notably the young Claude Debussy. Despite his happy family life (which included five children) and comfortable surroundings, as a composer Chausson was beset with crippling self-doubts. Struggling to express his feelings with as much emotional honesty and satisfying artistry as possible, he continually found himself “erupt[ing] with rage at seeing how what I can do is so far from what I would like to do, from what I seem to hear in my head” (from a letter of 1884). Friends ascribed the melancholy in his music to this obsessive search for what Vincent d’Indy called “the better,” to a profound empathy with the suffering of others, and to deep apprehension that critics would dismiss him merely as a wealthy amateur imitating Franck and Wagner—as indeed many did. Despite his insecurities, Chausson composed notable chamber and orchestral works, a substantial body of mélodies, and one opera, Le roi Arthus. Most observers believed that Chausson finally achieved his own voice in the late 1890s, especially in the Piano Quartet of 1897. Tragically, however, his career ended soon thereafter, on 10 June 1899: riding a bicycle at his country estate, he apparently lost control going down a hill and crashed head-first into a wall. Pierre Louÿs’s eloquent condolence letter to Mme. Chausson summed up the general reaction: “There was never a more excellent man . . . I was struck, each time, by the . . . admirable goodwill that radiated through each gesture. At every moment of his life, he felt compelled to bring happiness to people. Everyone loved him.” As his student Gustave Samazeuilh wrote, Chausson “will occupy an eminent place in the history of French music; a just recompense for a life devoted totally to the good, to work, and to the Ideal.”
Where is the western part of the Galactic Center Lobe located really?
Authors: Tsuboi Masato , Tsutsumi Takahiro , Kitamura Yoshimi , Miyawaki Ryosuke , Miyazaki Atsushi , Miyoshi Makoto 
Published: August 2020

Abstract
The Galactic Center Lobe (GCL) is a peculiar object widely protruding from the Galactic plane toward the positive Galactic latitude, which had been found toward the Galactic Center (GC) in the early days of the radio observation. The peculiar shape has suggested a relation with historical events, star burst, large explosion, and so on in the GC. However, the issue of whether the GCL is a single large structure located in the GC region is not yet settled conclusively. In the previous observations, the silhouette against the low-frequency emission was found in the western part of the GCL (WPGCL); this suggests that the part is located in front of the GC region. On the other hand, the Local Standard of Rest (LSR) velocity of the radio recombination line toward it was found to be as low as 0 km s−1. However, these observations cannot determine the exact position on the line-of-sight. There is still another possibility that it is in the near-side area of the GC region. In this analysis, we compare these results with the visual extinction map toward the GC. We found that the distribution of the visual extinction larger than 4 mag clearly corresponds to the silhouette of the WPGCL. The WPGCL must be located at most within a few kpc from us and not in the GC region. This would be a giant H ii region in the Galactic disk.
Revisiting the epoch of the earliest Chinese star catalog titled “Shi Shi Xing Jing”
Authors: Ahn Sang-Hyeon 
Published: August 2020

Abstract
The Shi Shi Xing Jing (SSXJ) is known to be the earliest star catalog in Chinese history. Its epoch of observation has long been a matter of debate. In recent studies, Sun Xiaochun pointed out that the observations must have been made using meridian instruments and developed a so-called Fourier method to determine the epoch, while Tsuko Nakamura developed a χ2 method to determine the epoch and showed that the measurement error can be estimated using bootstrap resamplings. However, they did not take both meridian measurements and bootstrap resamplings into consideration simultaneously. Hence, in this paper we determine the epoch and its uncertainty by applying the two methods and performing the bootstrap resamplings in a careful manner. We adopt identifications of the reference stars of 116 asterisms with stars in modern catalogs, including the determinative stars or the reference stars for the 28 lunar lodges. We find that the stars can be divided into four groups. Twenty-five of the 28 determinative stars are estimated to have been observed around 65 ± 28 BCE, corresponding to either Xianyu Wangren’s observation in 78–76 BCE or Geng Shouchang’s observation in 52 BCE. The other stars make three groups: the main group composed of 63 reference stars has an observation epoch of 108 ± 16 BCE corresponding to Luoxia Hong’s observation in 104 BCE; another group of eight reference stars including two determinative stars has an observation epoch of 200 ± 45 BCE, corresponding to the establishment of the Former Han dynasty; and the other group of 13 reference stars including one determinative star has an observation epoch of approximately 100 ± 35 CE, corresponding to the observations by ecliptic instruments in 103 CE following Gia Kui’s suggestion of 92 CE. In conclusion, the SSXJ has a few temporal strata of observations made through the Han dynasty.
Alterations in structure of biomolecules using ATR-FTIR and histopathological variations in brain tissue of Channa punctatus exposed to 2Naphthalene sufonate
Authors: Mehra Sukanya , Chadha Pooja 
Published: August 2020

Abstract
2Naphthalene sulfonate (2NS) is an intermediate compound used in textile industries. Being nonbiodegradable, the concerns regarding its biotoxicity have risen. In the present investigation the toxic effects of 2NS were analyzed with the help of Attenuated Total Reflection Fourier Transform Infrared (ATR-FTIR), which was used to monitor changes in the vibrational modes of functional groups within the biomolecules. After calculating LD 50, one half of LD 50 i.e. 0.33 mg/15 g b.w. was intraperitoneally administrated and the brain tissue was collected for investigation after 96 h of exposure. The spectra observed revealed the significant differences in absorbance and areas between control and treated groups reflecting the change in proteins, lipids and nucleic acid due to toxicity induced by 2NS. In addition, protein secondary structure analysis was focused in this study, which reveals alterations in α helix and β sheet structure after 2NS intoxication. Histopathology of brain was also studied, which reveals changes in the histology of brain in group treated with 2NS. In conclusion, the study highlighted the application of ATR-FTIR and histopathology for toxicity assessment.
Targeting the gut microbiota by Asian and Western dietary constituents: a new avenue for diabetes
Authors: Conteh Abdul Rahman , Huang Ruixue 
Published: August 2020

Abstract
Increasing numerous diabetes annually is a great concern in public health globally. Gut microbiota recently has been suggested to be an emerging organ acting as a critical regulator in diabetes. Notably, gut microbiota is closely affected through an individual’s nutrient intake and dietary pattern. Moreover, the metabolites of diets through gut microbiota are closely associated with the development of diabetes. Increasing evidence has established the association of different dietary pattern with alterations of the gut microbiota profile, in particular, the Asian diet and Western diet are typically as essential components linked to the interactions between gut microbiota and induction of obesity which is a significant risk factor for diabetes. In addition, some bacteria-related therapeutic methods including probiotics, dietary short-chain fatty acids immunotherapy, and gut microbiome transfer would be applied in the clinical prevention and control diabetes. Taken together, based on current published observations, the gut microbiota may serve as regulator or targets by the Asian diet and Western diet, contributing to the prevention or induction of diabetes eventually. In general, in the upcoming future, one of the emerging strategies for the prevention and control of diabetes may modulate gut microbiota through precise dietary strategies.
The evolutionary history and global spatio-temporal dynamics of potato virus Y
Authors: Gao Fangluan , Kawakubo Shusuke , Ho Simon Y W , Ohshima Kazusato 
Published: August 2020

Abstract
Potato virus Y (PVY) is a destructive plant pathogen that causes considerable losses to global potato and tobacco production. Although the molecular structure of PVY is well characterized, the evolutionary and global transmission dynamics of this virus remain poorly understood. We investigated the phylodynamics of the virus by analysing 253 nucleotide sequences of the genes encoding the third protein (P3), cylindrical inclusion protein (CI), and the nuclear inclusion protein (NIb). Our Bayesian phylogenetic analyses showed that the mean substitution rates of different regions of the genome ranged from 8.50 × 10−5 to 1.34 × 10−4 substitutions/site/year, whereas the time to the most recent common ancestor of PVY varied with the length of the genomic regions and with the number of viral isolates being analysed. Our phylogeographic analysis showed that the PVY population originated in South America and was introduced into Europe in the 19th century, from where it spread around the globe. The migration pathways of PVY correlate well with the trade routes of potato tubers, suggesting that the global spread of PVY is associated with human activities.