bluuebunny/crossref_metadata_2025_split huggingface dataset:
CS-6 A case of poorly differentiated chordoma with systemic metastasis
Authors: Shinojima Naoki , Harada Keisuke , Dekita Yuji , Yamamoto Haruaki , Itouyama Mai , Mikami Yoshiki , Mukasa Akitake 
Published: December 2021

Abstract
A case report: The patient was a 32-year-old man with diplopia. He was diagnosed as sphenoid sinusitis on MRI by a local doctor and visited an otolaryngologist. MRI showed extensive extension of neoplastic lesions from the clivus to the sphenoid sinus to the anterior ethmoid sinuses, bilateral cavernous sinuses, and the right medial and lateral pterygoid muscles. The right Lebiere’s lymph node was enlarged and thought to be a metastatic site. Based on the rapid growth and extension of the tumor, the patient was referred to the Department of Otolaryngology at our hospital on suspicion of sinonasal carcinoma. The possibility of chordoma could not be denied, so the patient was referred to our department. The patient underwent a joint endoscopic extended transsphenoidal tumor resection. The pathological diagnosis showed mitotic and necrotic features, and the majority of the cells showed highly atypical components without mucous substrate. However, brachyury, a marker for chordoma, was diffusely positive, and there was loss of INI1 (SMARCB1) expression. The final diagnosis was poorly differentiated chordoma. Postoperatively, the tumor in the right cavernous sinus grew rapidly, and the right eye became blind due to obstruction of the superior ophthalmic vein. The patient was treated with Gamma Knife as soon as possible in the hope of local control by high-dose irradiation, and after a total of three irradiations, the residual tumor shrank markedly and symptoms improved, but systemic metastasis occurred in a short period of time and the patient died. The number of cases of poorly differentiated chordoma has been reported rarely (more than 50), and it is more common in children and even rarer in adults. We report this case with a review of the literature.
COT-9 Prognostic impact of hypercoagulation in glioblastoma and molecular mechanism thereof
Authors: Negoto Tetsuya , Komaki Satoru , Moritsubo Mayuko , Furuta Takuya , Nakamura Hideo , Morioka Motohiro 
Published: December 2021

Abstract
Introduction: Pathological features of glioblastoma include intravascular thrombosis, suggesting that the thrombus formation in tumor microenvironment contributes to progression of gliomas. Meanwhile, glioblastoma has been known to be high risk malignant tumor for venous thromboembolism, however, it remains unclear how the coagulation-fibrinolysis system is disrupted, which essentially grow within the cranium in a localized manner, and how the disruption contributes to the malignant transformation.
Methods: Total 64 patients with glioblastoma between January 2014 and April 2021 who underwent a D-dimer test before the therapeutic intervention were divided into two groups: the high D-dimer group (D-dimer level &gt;3.0μg/ml) and the low D-dimer group (D-dimer level &lt;3.0μg/ml). We compared the two groups in the maximum gadolinium-enhanced MRI lesions, MIB-1 index, and gene abnormalities (IDH mutation, TERT promoter mutation, and MGMT promotor methylation). The progression-free survival (PFS) and overall survival were analyzed using the Kaplan-Meier method. Furthermore, in 23 patients who underwent a D-dimer test at recurrence, the time to death after recurrence was analyzed.
Results: The PFS in high D-dimer group was significantly shorter than that in the low D-dimer group (log-rank p = 0.0075). The D-dimer increase at the time of recurrence significantly correlated with the decrease in post-recurrence survival duration (log-rank p = 0.0226). Moreover, the gadolinium-enhanced lesions in the high D-dimer group were significantly larger.
Conclusion: The Pre-intervention D-dimer levels and PFS suggest that glioblastoma-induced systemic enhancement of the coagulation-fibrinolysis system plays a role in the malignant transformation. The D-dimer increase during the treatment was found to be a predictor of poor prognosis after recurrence. Furthermore, the MRI findings revealed a correlation between the D-dimer increase and the size of intratumoral necrosis. Meanwhile, no correlation with the MIB-1 index was found, suggesting that the mechanism of malignant transformation by hypercoagulation differ from enhanced cell proliferation.
Qurliqnoria (Mammalia: Bovidae) fossils from Qaidam Basin, Tibetan Plateau and deep-time endemism of the Tibetan antelope lineage
Authors: Tseng Z Jack , Wang Xiaoming , Li Qiang , Xie Guangpu 
Published: December 2021

Abstract
The Tibetan antelope (Pantholops hodgsonii) is an endemic bovid of the Tibetan Plateau, which was, until recently, considered an endangered species. Researchers have long speculated on the evolutionary origin of Pantholops, suggesting a connection to the rare fossil bovid Qurliqnoria. However, the lack of adequate fossil samples has prevented the testing of this deep-time endemism hypothesis for eight decades. Here, we report new fossils of Qurliqnoria cheni from the northern Tibetan Plateau, substantially increasing the amount of morphological data that can be brought to bear on the question of Tibetan antelope evolution. Phylogenetic analysis supports a Pantholops–Qurliqnoria clade and suggests that this lineage has been endemic to the Plateau for 11 Myr. Recent morphological and molecular studies that support the outgroup position of Pantholops relative to caprins (goats and relatives) and the fossil record of stem bovids from Europe together suggest that the Qurliqnoria–Pantholops lineage is likely to have dispersed to the Tibetan Plateau 15–11 Mya. Furthermore, the harsh environmental conditions to which Pantholops has adapted are likely to extend back to the time of its evolutionary origin. These findings provide an important new context for conservation management and research into the near-threatened Tibetan antelope, as the longest-living endemic member of the Tibetan Plateau fauna.
Cerebrovascular insulin receptors are defective in Alzheimerˈs disease
Authors: Leclerc M. , Bourassa P. , Tremblay C. , Caron V. , Sugère C. , Emond V. , Bennett D.A. , Calon F. 
Published: December 2021

AbstractCentral response to insulin is suspected to be defective in Alzheimer’s disease (AD), but its localization in the brain remains unknown. While most insulin is secreted in the bloodstream by the pancreas, how it interacts with the blood-brain barrier (BBB) to alter brain function remains poorly defined.Here, we show that human and murine cerebral insulin receptors (INSR), particularly the long isoform INSRα-B, are concentrated in microvessels rather than in the parenchyma. Vascular concentrations of INSRα-B were lower in the parietal cortex of subjects diagnosed with AD, positively correlating with cognitive scores, leading to a shift toward a higher INSRα-A/B ratio, consistent with cerebrovascular insulin resistance in the AD brain. Vascular INSRα was inversely correlated with β-amyloid (Aβ) plaques and β-site APP cleaving enzyme 1 (BACE1), but positively correlated with insulin-degrading enzyme (IDE), neprilysin and ABCB1. Using brain cerebral intracarotid perfusion, we found that the transport rate of insulin across the BBB remained very low (<0.03 µl.g-1.s-1) and was not inhibited by an INSR antagonist. However, intracarotid perfusion of insulin induced the phosphorylation of INSRβ which was restricted to microvessels. Such an activation of vascular INSR was blunted in 3xTg-AD mice, suggesting that AD neuropathology induces insulin resistance at the level of the BBB.Overall, the present data in postmortem AD brains and an animal model of AD indicate that defects in the INSR localized at the BBB strongly contribute to brain insulin resistance in AD, in association with Aβ pathology.HighlightsCirculating insulin activates brain insulin receptors in microvessels.BBB INSR contribute to cerebral insulin resistance in AD.Cognitive impairment in AD is associated with a loss of cerebrovascular INSRα-B.Loss of isoform INSRα-B is associated with increased BACE1 activity.SummaryLeclerc et al. show that circulating insulin activates cerebral insulin receptor localized on the blood-brain-barrier level (BBB), not in the parenchyma. Experiments with human brain samples and animal models provide evidence that INSR at the BBB are impaired in Alzheimer’s disease, thereby contributing to brain insulin resistance.
Tadr Is an Axonal Histidine Transporter Required for Visual Neurotransmission in Drosophila
Authors: Han Yongchao , Peng Lei , Wang Tao 
Published: December 2021

AbstractNeurotransmitters are generated by de novo synthesis and are essential for sustained, high-frequency synaptic transmission. Histamine, a monoamine neurotransmitter, is synthesized through decarboxylation of histidine by Histidine decarboxylase (Hdc). However, little is known about how histidine is presented to Hdc as a precursor. Here, we identified a specific histidine transporter, TADR (Torn And Diminished Rhabdomeres), that is required for visual transmission in Drosophila. TADR and Hdc co-localized to neuronal terminals, and mutations in tadr reduced levels of histamine, thus disrupting visual synaptic transmission and phototaxis behavior. These results demonstrate that a specific amino acid transporter provides precursors for monoamine neurotransmitters, providing the first genetic evidence that a histidine amino acid transporter plays a critical role in synaptic transmission. These results suggest that TADR-dependent local de novo synthesis of histamine is required for synaptic transmission.
Tibial nerve stimulation increases vaginal blood perfusion and bone mineral density and yield load in ovariectomized rat menopause model
Authors: Xu Jiajie Jessica , Zimmerman Lauren L. , Soriano Vanessa , Mentzelopoulos Georgios , Kennedy Eric , Bottorff Elizabeth C. , Stephan Chris , Kozloff Kenneth , Devlin Maureen J. , Bruns Tim M. 
Published: December 2021

ABSTRACTIntroduction and HypothesisHuman menopause transition and post-menopausal syndrome, driven by reduced ovarian activity and estrogen levels, are associated with an increased risk for symptoms including but not limited to sexual dysfunction, metabolic disease, and osteoporosis. Current treatments are limited in efficacy and may have adverse consequences, so investigation for additional treatment options is necessary. Previous studies have demonstrated that tibial nerve stimulation (TNS) or electro-acupuncture near the tibial nerve are minimally invasive treatments that increase vaginal blood perfusion or serum estrogen in the rat model. We hypothesized that TNS would protect against harmful reproductive and systemic changes associated with menopause.MethodsWe examined the effects of twice weekly TNS (0.2 ms pulse width, 20 Hz, 2x motor threshold) under ketamine-xylazine anesthesia in ovariectomized (OVX) female Sprague Dawley rats on menopause-associated physiological parameters including serum estradiol, body weight, blood glucose, bone health, and vaginal blood flow. Rats were split into three groups (n = 10 per group): 1) intact control (no stimulation), 2) OVX control (no stimulation), and 3) OVX stimulation (treatment group).ResultsTNS did not affect serum estradiol levels, body weight, or blood glucose. TNS transiently increased vaginal blood perfusion during stimulation for up to 5 weeks after OVX and increased areal bone mineral density and yield load of the right femur (side of stimulation) compared to the unstimulated OVX control.ConclusionTNS may ameliorate some symptoms associated with menopause. Additional studies to elucidate the full potential of TNS on menopause-associated symptoms under different experimental conditions are warranted.SummaryPercutaneous tibial nerve stimulation increases vaginal blood perfusion, areal bone mineral density, and femur yield load in an ovariectomized rat model of menopause.
A Computational Model of Stereoscopic Prey Capture in Praying Mantises”
Authors: O’Keeffe James , Nityananda Vivek , Read Jenny 
Published: December 2021

AbstractWe present a simple model which can account for the stereoscopic sensitivity of praying mantis predatory strikes. The model consists of a single “disparity sensor”: a binocular neuron sensitive to stereoscopic disparity and thus to distance from the animal. The model is based closely on the known behavioural and neurophysiological properties of mantis stereopsis. The monocular inputs to the neuron reflect temporal change and are insensitive to contrast sign, making the sensor insensitive to interocular correlation. The monocular receptive fields have a excitatory centre and inhibitory surround, making them tuned to size. The disparity sensor combines inputs from the two eyes linearly, applies a threshold and then an exponent output nonlinearity. The activity of the sensor represents the model mantis’s instantaneous probability of striking. We integrate this over the stimulus duration to obtain the expected number of strikes in response to moving targets with different stereoscopic distance, size and vertical disparity. We optimised the parameters of the model so as to bring its predictions into agreement with our empirical data on mean strike rate as a function of stimulus size and distance. The model proves capable of reproducing the relatively broad tuning to size and narrow tuning to stereoscopic distance seen in mantis striking behaviour. The model also displays realistic responses to vertical disparity. Most surprisingly, although the model has only a single centre-surround receptive field in each eye, it displays qualitatively the same interaction between size and distance as we observed in real mantids: the preferred size increases as prey distance increases beyond the preferred distance. We show that this occurs because of a stereoscopic “false match” between the leading edge of the stimulus in one eye and its trailing edge in the other; further work will be required to find whether such false matches occur in real mantises. This is the first image-computable model of insect stereopsis, and reproduces key features of both neurophysiology and striking behaviour.
Treatment of Recurrent Glioblastoma by Chronic Convection-Enhanced Delivery of Topotecan
Authors: Spinazzi Eleonora F. , Argenziano Michael G. , Upadhyayula Pavan S. , Banu Matei A. , Neira Justin A. , Higgins Dominique M.O. , Wu Peter B. , Pereira Brianna , Mahajan Aayushi , Humala Nelson , Al-Dalahmah Osama , Zhao Wenting , Save Akshay V. , Boyett Deborah M. , Marie Tamara , Furnari Julia L , Sudhakar Tejaswi D. , Stopka Sylwia A. , Regan Michael S. , Catania Vanessa , Good Laura , Behl Meenu , Jambawalikar Sachin , Mintz Akiva , Lignelli Angela , Agar Nathalie Y.R. , Sims Peter A. , Welch Mary , Lassman Andrew , Iwamoto Fabio , D’Amico Randy S. , Grinband Jack , Canoll Peter , Bruce Jeffrey N. 
Published: December 2021

ABSTRACTGlioblastoma, the most common primary brain malignancy, is invariably fatal. Systemic chemotherapy is ineffective mostly because of drug delivery limitations. To overcome this, we devised an internalized pump-catheter system for direct chronic convection-enhanced delivery (CED) into peritumoral brain tissue. Topotecan (TPT) by chronic CED in 5 patients with refractory glioblastoma selectively eliminated tumor cells without toxicity to normal brain. Large, stable drug distribution volumes were non-invasively monitored with MRI of co-infused gadolinium. Analysis of multiple radiographically localized biopsies taken before and after treatment showed a decreased proliferative tumor signature resulting in a shift to a slow-cycling mesenchymal/astrocytic-like population. Tumor microenvironment analysis showed an inflammatory response and preservation of neurons. This novel drug delivery strategy and innovative clinical trial paradigm overcomes current limitations in delivery and treatment response assessment as shown here for glioblastoma and is potentially applicable for other anti-glioma agents as well as other CNS diseases.
The p53 transactivation domain 1-dependent response to acute DNA damage in endothelial cells protects against radiation-induced cardiac injury
Authors: Kuo Hsuan-Cheng , Luo Lixia , Ma Yan , Williams Nerissa T. , da Silva Campos Lorraine , Attardi Laura D. , Lee Chang-Lung , Kirsch David G. 
Published: December 2021

AbstractThoracic radiation therapy can cause endothelial injury in the heart, leading to cardiac dysfunction and heart failure. Although it has been demonstrated that the tumor suppressor p53 functions in endothelial cells to prevent the development of radiation-induced myocardial injury, the key mechanism(s) by which p53 regulates the radiosensitivity of cardiac endothelial cells is not completely understood. Here, we utilized genetically engineered mice that express mutations in p53 transactivation domain 1 (TAD1) (p5325,26) or mutations in p53 TAD1 and TAD2 (p5325,26,53,54) specifically in endothelial cells to study the p53 transcriptional program that protects cardiac endothelial cells from ionizing radiation in vivo. p5325,26,53,54 loses the ability to drive transactivation of p53 target genes after irradiation while p5325,26 can induce transcription of a group of non-canonical p53 target genes, but not the majority of classic radiation-induced p53 targets critical for p53-mediated cell cycle arrest and apoptosis. After 12 Gy whole-heart irradiation, we found that both p5325,26 and p5325,26,53,54 sensitized mice to radiation-induced cardiac injury, in contrast to wild-type p53. Histopathological examination suggested that mutation of TAD1 contributes to myocardial necrosis after whole-heart irradiation, while mutation of both TAD1 and TAD2 abolishes the ability of p53 to prevent radiation-induced heart disease. Taken together, our results show that the transcriptional program downstream of p53 TAD1, which activates the acute DNA damage response after irradiation, is necessary to protect cardiac endothelial cells from radiation injury in vivo.
HLAncPred: A method for predicting promiscuous non-classical HLA binding sites
Authors: Dhall Anjali , Patiyal Sumeet , Raghava Gajendra P. S. 
Published: December 2021

AbstractIn the last two decades, ample of methods have been developed to predict the classical HLA binders in an antigen. In contrast, limited attempts have been made to develop methods for predicting binders for non-classical HLA; due to the scarcity of sufficient experimental data and lack of community interest. Of Note, non-classical HLA plays a crucial immunomodulatory role and regulates various immune responses. Recent studies revealed that non-classical HLA (HLA-E & HLA-G) based immunotherapies have many advantages over classical HLA based-immunotherapy, particularly against COVID-19. In order to facilitate the scientific community, we have developed an artificial intelligence-based method for predicting binders of non-classical HLA alleles (HLA-G and HLA-E). All the models were trained and tested on experimentally validated data obtained from the recent release of IEDB. The machine learning based-models achieved more than 0.98 AUC for HLA-G alleles on validation or independent dataset. Similarly, our models achieved the highest AUC of 0.96 and 0.88 on the validation dataset for HLA-E*01:01, HLA-E*01:03, respectively. We have summarized the models developed in the past for non-classical HLA binders and compared with the models developed in this study. Moreover, we have also predicted the non-classical HLA binders in the spike protein of different variants of virus causing COVID-19 including omicron (B.1.1.529) to facilitate the community. One of the major challenges in the field of immunotherapy is to identify the promiscuous binders or antigenic regions that can bind to a large number of HLA alleles. In order to predict the promiscuous binders for the non-classical HLA alleles, we developed a web server HLAncPred (https://webs.iiitd.edu.in/raghava/hlancpred), and a standalone package.Key PointsNon-classical HLAs play immunomodulatory roles in the immune system.HLA-E restricted T-cell therapy may reduce COVID-19 associated cytokine storm.In silico models developed for predicting binders for HLA-G and HLA-E.Identification of non-classical HLA binders in strains of coronavirusA webserver for predicting promiscuous binders for non-classical HLA allelesAuthor’s BiographyAnjali Dhall is currently working as Ph.D. in Bioinformatics from Department of Computational Biology, Indraprastha Institute of Information Technology, New Delhi, India.Sumeet Patiyal is currently working as Ph.D. in Bioinformatics from Department of Computational Biology, Indraprastha Institute of Information Technology, New Delhi, India.Gajendra P. S. Raghava is currently working as Professor and Head of Department of Computational Biology, Indraprastha Institute of Information Technology, New Delhi, India.
Effects of stimulus pulse rate on somatosensory adaptation in the human cortex
Authors: Hughes Christopher L , Flesher Sharlene N , Gaunt Robert A 
Published: December 2021

AbstractBackgroundIntracortical microstimulation (ICMS) of the somatosensory cortex can restore sensation to people with neurological diseases. However, many aspects of ICMS are poorly understood, including the effect of continuous stimulation on percept intensity over time.ObjectiveHere, we evaluate how tactile percepts, evoked by ICMS in the somatosensory cortex of a human participant adapt over time.MethodsWe delivered continuous and intermittent ICMS to the somatosensory cortex and assessed the reported intensity of tactile percepts over time in a human participant. Experiments were conducted across approximately one year and linear mixed effects models were used to assess significance.ResultsContinuous stimulation at high frequencies led to rapid decreases in intensity, while low frequency stimulation maintained percept intensity for longer periods. Burst-modulated stimulation extended the time before the intensity began to decrease, but all protocols ultimately resulted in complete sensation loss within one minute. Intermittent stimulation paradigms with several seconds between stimulus trains also led to decreases in intensity on many electrodes, but never resulted in extinction of sensation after over three minutes of stimulation. Additionally, longer breaks between each pulse train resulted in some recovery of the stimulus-evoked percepts. For several electrodes, intermittent stimulation had almost no effect on the perceived intensity.ConclusionsIntermittent ICMS paradigms were more effective at maintaining percepts, and given that transient activity in the somatosensory cortex dominates the response to object contact, this stimulation method may mimic natural cortical activity and improve the perception of stimulation over time.