bluuebunny/crossref_metadata_2025_split huggingface dataset:
MeCP2 gates spatial learning-induced alternative splicing events in the mouse hippocampus
Authors: Brito David V. C. , Gulmez Karaca Kubra , Kupke Janina , Frank Lukas , Oliveira Ana M. M. 
Published: November 2020

AbstractLong-term memory formation is supported by functional and structural changes of neuronal networks, which rely on de novo gene transcription and protein synthesis. The modulation of the neuronal transcriptome in response to learning depends on transcriptional and post-transcriptional mechanisms. DNA methylation writers and readers regulate the activity-dependent genomic program required for memory consolidation. The most abundant DNA methylation reader, the Methyl CpG binding domain protein 2 (MeCP2), has been shown to regulate alternative splicing, but whether it establishes splicing events important for memory consolidation has not been investigated. In this study, we identified the alternative splicing profile of the mouse hippocampus in basal conditions and after a spatial learning experience, and investigated the requirement of MeCP2 for these processes. We observed that spatial learning triggers a wide-range of alternative splicing events in transcripts associated with structural and functional remodeling and that virus-mediated knockdown of MeCP2 impairs learning-dependent post-transcriptional responses of mature hippocampal neurons. Furthermore, we found that MeCP2 preferentially affected the splicing modalities intron retention and exon skipping and guided the alternative splicing of distinct set of genes in baseline conditions and after learning. Lastly, comparative analysis of the MeCP2-regulated transcriptome with the alternatively spliced mRNA pool, revealed that MeCP2 disruption alters the relative abundance of alternatively spliced isoforms without affecting the overall mRNA levels. Taken together, our findings reveal that adult hippocampal MeCP2 is required to finetune alternative splicing events in basal conditions, as well as in response to spatial learning. This study provides new insight into how MeCP2 regulates brain function, particularly cognitive abilities, and sheds light onto the pathophysiological mechanisms of Rett syndrome, that is characterized by intellectual disability and caused by mutations in the Mecp2 gene.
Circular RNA MCTP2 inhibits cisplatin resistance in gastric cancer by miR-99a-5p-mediated induction of MTMR3 expression
Authors: Sun Guangli , Li Zheng , He Zhongyuan , Wang Weizhi , Wang Sen , Zhang Xing , Cao Jiacheng , Xu Penghui , Wang Haixiao , Huang Xiaoxu , Xia Yiwen , Lv Jialun , Xuan Zhe , Jiang Tianlu , Fang Lang , Yang Jing , Zhang Diancai , Xu Hao , Xu Zekuan 
Published: November 2020

AbstractBackgroundCisplatin (CDDP) is the first-line chemotherapy for gastric cancer (GC). The poor prognosis of GC patients is partially due to the development of CDDP resistance. Circular RNAs (circRNAs) are a subclass of noncoding RNAs that function as microRNA (miRNA) sponges. The role of circRNAs in CDDP resistance in GC has not been evaluated.MethodsRNA sequencing was used to identify the differentially expressed circRNAs between CDDP-resistant and CDDP-sensitive GC cells. qRT-PCR was used to detect the expression of circMCTP2 in GC tissues. The effects of circMCTP2 on CDDP resistance were investigated in vitro and in vivo. Pull-down assays and luciferase reporter assays were performed to confirm the interactions among circMCTP2, miR-99a-5p, and myotubularin-related protein 3 (MTMR3). The protein expression levels of MTMR3 were detected by western blotting. Autophagy was evaluated by confocal microscopy and transmission electron microscopy (TEM).ResultsCircMCTP2 was downregulated in CDDP-resistant GC cells and tissues compared to CDDP-sensitive GC cells and tissues. A high level of circMCTP2 was found to be a favorable factor for the prognosis of patients with GC. CircMCTP2 inhibited proliferation while promoting apoptosis of CDDP-resistant GC cells in response to CDDP treatment. CircMCTP2 was also found to reduce autophagy in CDDP-resistant GC cells. MiR-99a-5p was verified to be sponged by circMCTP2. Inhibition of miR-99a-5p could sensitize GC cells to CDDP. MTMR3 was confirmed to be a direct target of miR-99a-5p. Knockdown of MTMR3 reversed the effects of circMCTP2 on the proliferation, apoptosis and autophagy of CDDP-resistant GC cells. CircMCTP2 was also confirmed to inhibit CDDP resistance in vivo in a nude mouse xenograft model.ConclusionsCircMCTP2 sensitizes GC to CDDP through the upregulation of MTMR3 by sponging miR-99a-5p. Overexpression of CircMCTP2 could be a new therapeutic strategy for counteracting CDDP resistance in GC.
A versatile toolkit for CRISPR-Cas13-based RNA manipulation in Drosophila
Authors: Huynh Nhan , Depner Noah , Larson Raegan , King-Jones Kirst 
Published: November 2020

AbstractAdvances in CRISPR technology have immensely improved our ability to manipulate nucleic acids, and the recent discovery of the RNA-targeting endonuclease Cas13 adds even further functionality. Here, we show that Cas13 works efficiently in Drosophila, both ex vivo and in vivo. We test 44 different Cas13 variants to identify enzymes with the best overall performance and show that Cas13 could target endogenous Drosophila transcripts in vivo with high efficiency and specificity. We also develop Cas13 applications to edit mRNAs and target mitochondrial transcripts. Our vector collection represents a versatile tool collection to manipulate gene expression at the post-transcriptional level.
Cohort profile: why do people keep hurting their back?
Authors: Klyne David M. , van den Hoorn Wolbert , Barbe Mary F. , Cholewicki Jacek , M. Hall Leanne , Khan Asaduzzaman , Meroni Roberto , Moseley G. Lorimer , Nicholas Michael , O’Sullivan Lee , Park Rachel , Russell Glen , Sterling Michele , Hodges Paul W. 
Published: November 2020

Abstract
Objective
Low back pain (LBP) is one of the most disabling and costly conditions worldwide. It remains unclear why many individuals experience persistent and recurrent symptoms after an acute episode whereas others do not. A longitudinal cohort study was established to address this problem. We aimed to; (1) evaluate whether promising and potentially modifiable biological, psychological, social and behavioural factors, along with their possible interactions, predict LBP outcome after an acute episode; (2) compare these factors between individuals with and without acute LBP; and (3) evaluate the time-course of changes in these factors from LBP onset. This paper outlines the methodology and compares baseline characteristics between acute LBP and control, and LBP participants with and without follow-up.

Results
133 individuals with acute LBP and 74 pain-free individuals participated. Bio-psycho-social and behavioural measures were collected at baseline and 3-monthly for 12 months (LBP) or 3 months (control). Pain and disability were recorded fortnightly. Baseline characteristics were mostly similar between those who did and did not return for follow-up. Initial analyses of this cohort have revealed important insights into the pathways involved in acute-to-chronic LBP. These and future findings will provide new targets for treatment and prevention of persistent and recurrent LBP.
Genetic counselling and testing for inherited dementia: single-centre evaluation of the consensus Italian DIAfN protocol
Authors: Mega Anna , Galluzzi Samantha , Bonvicini Cristian , Fostinelli Silvia , Gennarelli Massimo , Geroldi Cristina , Zanetti Orazio , Benussi Luisa , Di Maria Emilio , Frisoni Giovanni B. 
Published: November 2020

Abstract
Background
A consensus protocol for genetic counselling and testing of familial dementia, the Italian Dominantly Inherited Alzheimer’s and Frontotemporal Network (IT-DIAfN) protocol, has been developed in Italy by a network of expert dementia centres. The aim of this study is to evaluate feasibility and acceptability of the genetic counselling and testing process, as undertaken according to the IT-DIAfN protocol in one of the IT-DIAfN dementia research centres.

Methods
The protocol was tested by a multidisciplinary team at the IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy, on affected individuals with suspected inherited forms of Alzheimer’s disease (AD) or frontotemporal dementia (FTD), and to healthy at-risk relatives. The genetic counselling and testing process consisted of (i) pre-test consultation and psychological assessment (ii) genetic testing, (iii) genetic test result disclosure and (iv) follow-up consultation and psychological assessment.

Results
Twenty affected individuals from 17 families fulfilled the family history criteria of the IT-DIAfN protocol for suspected inherited dementia (17 for AD, 2 for FTD, 1 for inclusion body myopathy with Paget disease of bone and frontotemporal dementia) and were included in the protocol. Nineteen out of 20 affected individuals received the genetic test result (one left after the pre-test consultation being not ready to cope with an unfavourable outcome). A pathogenic mutation was found in 6 affected individuals (1 in PSEN1, 2 in PSEN2, 1 in GRN, 1 in MAPT, 1 in VCP). Eleven healthy at-risk relatives asked to undergo predictive testing and were included in the protocol. Three completed the protocol, including follow-up; one did not ask for the genetic test result after genetic testing; and eight withdrew before the genetic testing, mainly due to an increased awareness about the possible consequences of an unfavourable test result. To date, no catastrophic reactions were reported at the follow-up.

Conclusions
Our case series shows that a structured genetic counselling and testing protocol for inherited dementia can be implemented in both affected individuals and at-risk relatives in a research setting. The procedure was shown to be safe in terms of occurrence of catastrophic events. A formal validation in larger cohorts is needed.
Automatic LIDAR building segmentation based on DGCNN and euclidean clustering
Authors: Gamal Ahmad , Wibisono Ari , Wicaksono Satrio Bagus , Abyan Muhammad Alvin , Hamid Nur , Wisesa Hanif Arif , Jatmiko Wisnu , Ardhianto Ronny 
Published: November 2020

AbstractThere has been growing demand for 3D modeling from earth observations, especially for purposes of urban and regional planning and management. The results of 3D observations has slowly become the primary source of data in terms of policy determination and infrastructure planning. In this research, we presented an automatic building segmentation method that directly uses LIDAR data. Previous works have utilized the CNN method to automatically segment buildings. However, the existing body of works have relied heavily on the conversion of LIDAR data into Digital Terrain Model (DTM), Digital Surface Model (DSM), or Digital Elevation Model (DEM) formats. Those formats required conversion of LIDAR data into raster images, which poses challenges to the evaluation of building volumes. In this paper, we collected LIDAR data with unmanned aerial vehicle and directly segmented buildings utilizing the said LIDAR data. We utilized a Dynamic Graph Convolutional Neural Network (DGCNN) algorithm to separate buildings and vegetation. We then utilized Euclidean Clustering to segment each building. We found that the combination of these methods are superior to prior works in the field, with accuracy up to 95.57% and an Intersection Over Union (IOU) score of 0.85.
Evaluation of a multidisciplinary global health online course in Mexico
Authors: Carrasco Héctor , Fuentes Patricia , Eguiluz Itzel , Lucio-Ramírez Cesar , Cárdenas Sandra , Leyva Barrera Ilse Mariana , Pérez-Jiménez Manuel 
Published: November 2020

Abstract
Background
Global Health Education (GHE) focuses on training proactive global citizens to tackle health challenges in an increasingly interconnected and interdependent world. Studies show that health professionals in training have reported that GHE has improved their teamwork, responsiveness to contextual factors that impact health, and understanding of health systems; however, there is little research on the impact of GHE courses in undergraduate settings, especially in low and middle-income countries (LMICs).

Methods
Our study analyzes a multidisciplinary online global health course at Tecnologico de Monterrey, México. We conducted a cross-sectional study with pre- and post-design. Students who took the multidisciplinary course of Global Health for Leaders in the Fall of 2019 (n = 153) and Spring of 2020 (n = 348) were selected for this study. Using a five-point Likert scale (strongly agree to strongly disagree), the survey assessed seven competencies as well as questions about course expectations, takeaways, and recommendations to improve the course. We performed descriptive statistical analyses comparing the combined pre-tests (from Fall and Spring cohorts) to the combined post-tests. Fisher’s exact test was used to compare the samples.

Results
Of the 501 pre-course surveys administered, 456 responses were completed in the pre-course and 435 in the post-course (91% overall response rate). Only 8.7% of the respondents in the pre-course survey strongly agreed that they could describe fundamental aspects of global health such as the Millennium Development Goals or Sustainable Development Goals, in contrast to a 56% of the students who strongly agreed in the post-course survey (p < 0.001). Similar differences were captured in understanding the global burden of disease, social determinants of health, the effects of globalization in health, health systems’ goals and functions, and human rights. 38% felt that the course helped them develop a more empathetic perception of the suffering of others experiencing global health-related issues.

Conclusion
In this study, we have presented our experience in teaching an online global health course for multidisciplinary undergraduates in a LMIC. The competencies reported by our students indicate that the course prepared them to confront complex global health issues.
PET/CT imaging for tumour response assessment to immunotherapy: current status and future directions
Authors: Unterrainer Marcus , Ruzicka Michael , Fabritius Matthias P. , Mittlmeier Lena M. , Winkelmann Michael , Rübenthaler Johannes , Brendel Matthias , Subklewe Marion , von Bergwelt-Baildon Michael , Ricke Jens , Kunz Wolfgang G. , Cyran Clemens C. 
Published: November 2020

AbstractRecent immunotherapeutic approaches have evolved as powerful treatment options with high anti-tumour responses involving the patient’s own immune system. Passive immunotherapy applies agents that enhance existing anti-tumour responses, such as antibodies against immune checkpoints. Active immunotherapy uses agents that direct the immune system to attack tumour cells by targeting tumour antigens. Active cellular-based therapies are on the rise, most notably chimeric antigen receptor T cell therapy, which redirects patient-derived T cells against tumour antigens. Approved treatments are available for a variety of solid malignancies including melanoma, lung cancer and haematologic diseases. These novel immune-related therapeutic approaches can be accompanied by new patterns of response and progression and immune-related side-effects that challenge established imaging-based response assessment criteria, such as Response Evaluation Criteria in Solid tumours (RECIST) 1.1. Hence, new criteria have been developed. Beyond morphological information of computed tomography (CT) and magnetic resonance imaging, positron emission tomography (PET) emerges as a comprehensive imaging modality by assessing (patho-)physiological processes such as glucose metabolism, which enables more comprehensive response assessment in oncological patients. We review the current concepts of response assessment to immunotherapy with particular emphasis on hybrid imaging with 18F-FDG-PET/CT and aims at describing future trends of immunotherapy and additional aspects of molecular imaging within the field of immunotherapy.
German guidelines on the diagnosis and treatment of neurosyphilis
Authors: Klein Matthias , Angstwurm Klemens , Esser Stefan , Hahn Kathrin , Maschke Matthias , Scheithauer Simone , Schoefer Helmut , Sturzenegger Matthias , Wildemann Brigitte , Weber Jörg 
Published: November 2020

AbstractIntroductionIn view of the importance of neurosyphilis and the difficulties encountered in diagnosing it, the S1 guideline “Neurosyphilis” has been published by the German Society for Neurology (DGN) in accordance with the stipulations of the Association of the Scientific Medical Societies in Germany (AWMF). The present article is an abridged translation of that German guideline.Main recommendations(a) Neurosyphilis can manifest as early neurosyphilis (meningitis, meningovascular neurosyphilis or syphilitic gummas) or late neurosyphilis (tabes dorsalis, general paresis). (b) The following diagnostic criteria help to establish the presence of probable neurosyphilis (always point iv, accompanied by any two of points i to iii): (i) subacute or chronic neuro-psychiatric symptoms; (ii) increased cerebrospinal fluid (CSF) cell count or signs of blood–CSF barrier disruption; (iii) positive effect of anti-neurosyphilis antibiotic therapy on clinical course and CSF findings; (iv) positive TPHA/TPPA or FTA test in serum. (c) The diagnosis of neurosyphilis is confirmed by the subsequent detection of intrathecal production of antibodies againstTreponema pallidum. (d) In neurosyphilis, treatment with intravenous penicillin or ceftriaxone for 14 days is recommended. (e) The following parameters can be used to assess a therapeutic effect: clinical findings, serum VDRL, and CSF cell count.ConclusionThe German guideline on the diagnosis and treatment of neurosyphilis is a practical tool to support clinicians in diagnosing and treating patients with neurosyphilis. This article is an abridged translation of this guideline (Klein MW, J.; Angstwurm, K.; Esser, S.; Hahn, K.; Matschke, M.; Scheithauer, S.; Schoefer, H.; Sturzenegger, M.; Wildemann, B. Neurosyphilis, S1-Leitlinie. Deutsche Gesellschaft für Neurologie, Leitlinien für Diagnostik und Thearpie in der Neurologie 2020).
A systematic review of the prevalence of mental and neurocognitive disorders amongst older adults’ populace in Egypt
Authors: Odejimi Opeyemi , Tadros George , Sabry Noha 
Published: November 2020

Abstract
Background
Mental and neurocognitive disorders are the leading cause of disabilities amongst the older adult populace worldwide. The population of the older adult in Egypt is fast growing. The national census in 2017 revealed a 2.56% increase in the older adult population from the 2006 census, and these figures are expected to double by year 2031. This study aims to review current evidence about the prevalence of mental and neurocognitive disorders amongst older adult population in Egypt.

Results
A systematic review was carried out, and 16 studies met the inclusion criteria outlined in this study. Four main mental and neurocognitive disorders were identified: depression, anxiety, cognitive impairment and dementia. The reported prevalence of depression, anxiety, dementia and cognitive impairment are 23.7–74.5%, 14.2–72%, 3.66–39.2% and 1.74–51.4%, respectively. Anxiety and depression were positively correlated with the female gender, increasing age and lower educational status. Also, cognitive impairment and dementia were positively correlated with age, illiteracy or low education. However, there appears to be inconsistencies in the diagnostic tools used.

Conclusion
Egypt aging population is growing, and this research brings to forefront the scale of mental and neurocognitive disorders amongst the older adult population. This may help ensure evidence-based initiatives are put in place and priority is given to resource allocation for geriatric mental and neurocognitive disorders in Egypt.

Systematic review registration
PROSPERO CRD42018114831
Omental Metastasis from ALK-positive Lung Cancer — A Case Report
Authors: Khalid Taha , Phelan Brendan , Yousif Ala 
Published: November 2020

Abstract
Background
Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide. In Ireland alone, there are over 2500 new cases of lung cancer diagnosed each year. It ranks fourth among the most common cancers and causes 21% of all cancer-related deaths.
Lung cancers usually metastasize to the liver, brain, bone, and adrenal glands—rarely affecting the abdomen. To our knowledge, there are 8 previous studies in the literature to date which involve omental metastasis from NSCLC.

Case presentation
A 73-year-old lady presented with a history of productive cough for 18 months. A chest X-ray showed a suspicious 6 cm mass in the right lower zone. She went on to have an endobronchial biopsy which confirmed a moderately differentiated adenocarcinoma of the lung which was ALK positive. She went on to have staging PET and CT scans and was staged as cT3N2M0. She was not a suitable candidate for surgery so she had radical chemo-radiotherapy with 4 cycles of cisplatin pemetrexed followed by radical dose sequential radiotherapy. Post treatment CT showed the tumor to be more spiculated in appearance. She was ineligible for Durvalumab maintenance therapy due to the extensive pneumonitis following her radiotherapy which required a prolonged course of steroids. Interval scans every 3 months did not show any progression of disease.
She presented to the hospital 13 months post her diagnosis with progressive abdominal swelling. Restaging CT scans showed extensive omental infiltration, the presence of multiple peritoneal nodules, and progression of her pulmonary disease with new brain metastasis. Cytological analysis of the ascitic fluid confirmed metastasis followed by omental biopsy which confirmed metastatic ALK-positive NSCLC. She went on to have targeted treatment with alectinib. She tolerated the treatment well. Restaging scans done 3 months later showed good partial response to therapy.

Conclusion

In conclusion, ALK-positive NSCLC with metastasis to the omentum is very rare. However, in patients with atypical symptoms like ascites, the possibility of a metastasis must be considered and repeat biopsy is always recommended. A targeted therapy in the selected patients has shown a more durable response than chemotherapy.
Walking a Tightrope: Dosage Modifications and Treatment Outcomes of All-Trans-Retinoic Acid, Arsenic Trioxide, and Daunorubicin for High-Risk Acute Promyelocytic Leukemia
Authors: Danthala Madhav , Golamari Krishna Reddy , Seshachalam Arun , Mikkilineni Anupama , Chappidi Sitalata , Mekala Mahesh Babu , Elangovan Vidhubala , Chinnakali Palanivel 
Published: November 2020

PURPOSE The use of all- trans-retinoic acid (ATRA) and arsenic trioxide (ATO) in the treatment of low- and intermediate-risk acute promyelocytic leukemia (APL) is the standard of care. We report the combined use of ATRA, ATO, and daunorubicin (DNR) in patients newly diagnosed with high-risk APL. The primary focus was to describe the drug dosage modifications made in the real-world scenario. METHODS In this descriptive study, we included 16 out of 28 patients with high-risk APL from two tertiary care centers in South India (Vijayawada and Trichy) between January 2015 and December 2018. A unique approach of initiating ATRA at a dose of 25 mg/m2 on day 1 and escalation to 45 mg/m2 after cytoreduction with DNR and hydroxyurea was followed in all patients to avert differentiation syndrome, in the setting of hyperleukocytosis at presentation. RESULTS All patients who survived the first 3 days of admission achieved complete remission after a median duration of 29 days. There were no deaths during induction or consolidation, and the regimen was well tolerated; two patients developed grade 3/4 peripheral neuropathy requiring treatment modification. After a median follow-up duration of 1.9 years, there were no hematologic or molecular relapses. CONCLUSION The study sheds light on the modifications made to recommended dosages of ATRA, ATO, and DNR to optimize outcomes in high-risk APL and reaffirms the importance of ATO use in the front-line setting to achieve durable responses with minimal toxicity.