bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selective Targeting of Class1 Histone Deacetylase (HDAC) Isoforms by a Novel Inhibitor SBAK-GHA Potently Resist Leukemogenesis
Authors: Bhat Javeed Ahmad , Dar Nawab John , Ahmad Mudassier , Mintoo Mubashir Javed , Najar Rauf Ahmad , Capalash Neena , Mondhe Dilip Manikrao , Sharma Simmi , Shah Bhahwal Ali , Hamid Abid , Khan Mohammad Imran 
Published: August 2020

Abstract
Background: Acute promyelocytic leukemia (APL) and acute lymphoblastic leukaemia (ALL) are often presented with loss of H4K16 monoacetylation (ac) and H4K20 trimethylation (3Me) due to increased activity of Class I HDAC’s. In the current study we explored the efficacy and mechanistic basis of a novel Class I HDAC inhibitor SBAK-GHA across different leukemic cell lines and characterised the distinct acetylation pattern on histone H3 and H4.Methods: We initially performed general and class specific HDAC enzyme activity assays to establish the effect of our lead molecule SBAK-GHA. Following, we have probed various acetylation sites to understand a thorough acetylation profile of various leukemic cell lines by immunoblotting. Next, to understand the effect of various Class 1 HDAC isoforms on acetylation levels of hallmark proteins in leukaemia; lentiviral knockdown approach was carried out. In addition, cell cycle analysis was also done to distinguish the pattern of cell cycle phase arrest, followed by Chip-qPCR studies of various cyclins and their relationship with cell cycle arrest. Finally, an in vivo study was performed to confirm the anti-leukemic activity of SBAK-GHA by using specific leukaemia models.Results: SBAK-GHA showed class I HDAC inhibitor activity specifically targeting HDAC 2. SBAK-GHA treatment upregulates H4K16 ac and H4K20 me3 in variety of leukemic cell lines. Similar results were found during knock down of HDAC2 in leukemic cell lines. Moreover, we also observed a coherence of events like cell cycle arrest across different cell types of leukemias and modulation in the levels of acetylation across different cyclin promoters. Further on, studies in various in vivo cancer models demonstrated SBAK-GHA to be highly selective towards lymphocytic leukaemia.Conclusion: Our data provided a basic overview of relationship between different class I HDAC isoforms and their possible roles in regulation of histone acetylation in pathogenesis of leukaemia. Our study here presented multiple evidences regarding SBAK-GHA as a novel HDAC2 inhibitor. SBAK-GHA resist leukemogenesis mainly by inducing the repressed H4K16 ac and H4K20 me3. Further, the results in present study had established a relationship between class I HDAC isoforms and their possible roles in regulation of histone acetylation in pathogenesis of leukaemia.
MUC3A Promotes Non-Small Cell Lung Cancer Progress via Activating NFκB Pathway and Attenuates Radiosensitivity
Authors: Sun Yingming , Sun Xiaoge , You Chengcheng , Ma Shijing , Luo Yuan , Peng Shan , Tang Fang , Tian Xiaoli , Wang Feng , Huang Zhengrong , Yu Hongnv , Xiao Yu , Wang Xiaoyong , Zhang Junhong , Gong Yan , Xie Conghua 
Published: August 2020

Abstract
Background: MUC3A is highly expressed in lung adenocarcinoma, but its functions and effects on clinical outcomes are not well understood.Methods: Tissue microarray was used to analysis the relathionship between MUC3A and clinicalpathological charcristics of lung adenocarcinoma; Colony formation and MTT array ware used to detect cell proliferation; WB applied to investigate the protein amount; Transwell was applied to evaluate cell invasion; IF was used to observe the location and expression of targeted proteins; IP was use to prove the binding of proteins. Mcherry-GFP-LC3 II adenovirus and TEM were performed to observe cell autophagy. Xnograft mouse model were used to investigate the effect of MUC3A in vivo.Result: 92 patients’ tumor samples indicated that high expression of MUC3A was associated with poor prognosis, advanced staging, and low differentiation. Co-immunoprecipitation results revealed that MUC3A interacted with RELA. MUC3A activated the NFκB pathway via promoting RELA phosphorylation and interfering the binding of RELA to IκB. MUC3A knockdown significantly suppressed cell proliferation and induced G1 arrest. MUC3A deficiency increased radiation-induced DNA double strain breaks via impairing the BRCA-1/RAD51 pathway and nuclear translocation of P53 and XCRR6. Moreover, MUC3A deficiency induced autophagy in lung cancer cells. MUC3A knockdown significantly suppressed tumor growth in xenograft model and had a synergistic effect with radiation. Less nuclear translocation of RELA and P53 was also observed in tumor tissue in vivo.Conclusion: MUC3A was a potential oncogene, and its high expression was associated with unfavorable clinical outcomes. Patient with high expression of MUC3A should be more frequent follow-up and might benefit less from radiotherapy.
K-RAS, B-RAF and GNAS Gene Status and Immunohistochemistry Analysis of Mucinous Neoplasm of Appendix
Authors: ren xinyu , Cheng Yin , Lu Tao , Lu Junliang , Wu Yan , Pang Junyi , Chen Longyun , Zhou Weixun , Liang Zhiyong 
Published: August 2020

Abstract
AIM

Low grade appendiceal mucinous neoplasm (LAMN) and serrated lesions are sometimes hard to differentiate from morphology. We try to characterize them from the immunohistochemical and molecular perspective and to reflect the difference between them.
METHODS

25 appendix neoplasm including 13 LAMNs, 12 serrated lesions were selected from January 2013 to December 2014. Immunohistochemical analyses for cytokeratin 20, MUC6, MUC5AC, MUC1, Ki-67, P53 and mismatch repair (MMR) proteins including MLH1, PMS-2, MSH-6, MSH-2 were performed. Microsatellite instability (MSI) status was also evaluated. Besides, we detect K-RAS, B-RAF and GNAS gene mutation status of these lesions.
RESULTS

Immunochemically, 83.3% serrated lesions showed scattered CK20 staining in the deep crypt, which was less so for LAMNs. As for mucin expression, MUC5AC had slightly higher positive rate in LAMNs and than in serrated lesions.MUC1 was significantly higher expressed in LAMNs than in serrated lesions. 46.1% LAMNs have P53 expression in deep crypt, while P53 was negative in the deep crypt of serrated lesions. 58.3% serrated lesions had deficient MMR protein expresion pattern compared to 23.1% of LAMNs. B-RAF mutation was detected in 3 cases, all were serrated lesions. K-ras and GNAS mutation was detected in both LAMNs and serrated lesions.
CONCLUSION

Immunohistochemical panel comprising markers such as CK20, MUC5AC, MUC1, Ki-67 and P53, with genotyping covering hotspots of the KRAS, BRAF and GNAS genes can help the differential diagnosis of low grade appendix neoplasm.
Multimodal Prehabilitation in Patients with Non-Small Cell Lung Cancer Undergoing Anatomical Resection: Protocol of a Non-Randomised Feasibility Study
Authors: Molenaar Charlotte Johanna Laura , Von Meyenfeldt Erik Martin , de Betue Carlijn Tini Ireen , Schep Goof , Soud Magdolen Youssef El , Thiel Eric van , Rademakers Nicky , Hoornweg Sanne Charlotte , Slooter Gerrit Dirk , Broek Frank van den , Marres Geertruid Marie Heleen 
Published: August 2020

Abstract
BackgroundThe preoperative period can be used to enhance a patient’s functional capacity with multimodal prehabilitation and, consequently improve and fasten postoperative recovery. Especially non-small cell lung cancer (NSCLC) surgical patients may benefit from this intervention, since the affected and resected organ is an essential part of the cardiorespiratory fitness. Drafting a prehabilitation programme is a challenge, since many disciplines are involved, and time between diagnosis of NSCLC and surgery is limited. We designed a multimodal prehabilitation programme prior to pulmonary surgery and conduct a study to assess feasibility and efficacy of the programme. Publication of this protocol may help other health care facilities to implement such a programme. MethodsThe multimodal prehabilitation programme consists of an exercise programme, nutritional support, mental support, smoking cessation programme, patient empowerment and respiratory optimisation. In two Dutch teaching hospitals, 40 adult patients with proven or suspected NSCLC will be included. In a non-randomised fashion, 20 patients follow the multimodal prehabilitation programme and 20 will be assessed in the control group, according to patient preference. Assessments take place at four time points: baseline, week before surgery, six weeks postoperatively and three months postoperatively. Feasibility and efficacy of the prehabilitation programme will be assessed as primary outcomes. DiscussionSince the time between diagnosis of NSCLC and surgery is limited, it is a challenge to implement a prehabilitation programme. This study will assess whether this is feasible and effective. The non-randomised fashion of the study might result in a selection bias. However, the control group is necessary, to put the prehabilitation group in perspective and to assess feasibility further. By publishing this protocol of our feasibility study, we aim to facilitate others to evaluate and implement a multimodal prehabilitation programme for surgical lung cancer patients.Trial registrationThis feasibility study is registered as NL8080 in the Netherlands Trial Register on the 10th of October 2019, https://www.trialregister.nl/trial/8080. Secondary identifiers: CCMO (Central Committee on Research Involving Human Subjects) number NL70578.015.19, reference number of the Medical Ethical Review Committee of Máxima MC W19.045.
Age, Gender, Height and Weight in Relation to Joint Cartilage Thickness Among School-aged Children From Ultrasonographic Measurement
Authors: Gau Chunchun , Yao Tsung-Chieh , Gan Shu-Ting , Lin Syh-Jae , Yeh Kuo-Wei , Chen Li-Chen , Ou Liang- Shiou , Lee Wen-Yi , Wu Chao-Yi , Huang Jing-Long 
Published: August 2020

Abstract
Background: Among school-age children, the decrease of cartilage thickness (Cth) with increasing age is well known. However, the influence of body mass index (BMI), height or weight on Cth has not been revealed. Here in, we aim to establish an age- and gender-specific Cth standard reference among Asians and investigate the possible prestige of BMI, height and weight. Methods: A cross-sectional study was performed in healthy Asian children. Bilateral knees, ankles, wrists, second metacarpophalangeals (MCPs) and proximal interphalangeals (PIPs) were measured using ultrasound. The children’s height, weight and BMI were also recorded for later adjustment.Results: A total of 200 school age Asian children (including 86 girls and 114 boys, aged between 5 to 13 years-old) were investigated. Cth differences were observed in the knees, ankles, wrists, MCPs and PIPs between sexes (p<0.05), with girls having thinner cartilage thickness. While Cth decreases with increasing age ( p <0.0001, 0.039, 0.001, 0.023, 0.091 in girls’ knees, ankles, wrists, MCPs and PIPs and p = 0.002, 0.001, <0.0001, 0.001, 0.045 in boys’, respectively). Our data showed that weight, height and BMI are not the main factors contributing to Cth. A formula to calculate gender-specific cartilage thickness for Asian school age children is suggested. There was no difference in Cth after adjusting for height or weight between Asian or Caucasian group.Conclusions: A formula to calculate gender-specific cartilage thickness for Asian school age children is suggested. Height, weight and BMI were not the major contributor for Cth among school age children.
Paludification reduces black spruce growth rate but does not alter ecophysiological mechanisms in Canadian boreal forested peatlands
Authors: Beaulne Joannie , Boucher Étienne , Garneau Michelle , Magnan Gabriel 
Published: August 2020

Abstract
Background Paludification is widespread in the boreal biome, inducing tree growth decline in forested peatlands following the development of thick organic layers over the mineral soil. However, the ecophysiological processes involved remain poorly documented and little is known about the interactions between tree growth mechanisms and site conditions in these ecosystems. We investigated changes in stem growth and main ecophysiological processes in a black spruce forested peatland in eastern Canada by combining peat-based and tree-ring stable isotope analyses. These were conducted at three sampling sites located along a paludification gradient with different peat thicknesses.Results Organic layer thickening induces black spruce growth decline without altering tree ecophysiological mechanisms. A 40% increase in water use efficiency, or the ratio of carbon assimilated to water losses, was observed at the three sites from 1920 to the 1980s, but did not translate into enhanced tree growth. A clear shift in the 1980s revealed a decline in black spruce sensitivity to climate and rising atmospheric CO2 concentration, regardless of the organic layer thickness. Water table reconstructions revealed an important drawdown in the last few decades at the three sites, but we found no evidence of an influence of water table variations on stem growth.Conclusions This study shows that paludification induces black spruce growth decline without altering tree metabolism in boreal forested peatlands. This underlines that changes in water use efficiency are decoupled from changes in carbon allocation, which are constrained by site, or even tree-specific strategies to access water and nutrients from belowground. Our findings indicate that dynamic changes in edaphic conditions need to be considered in process models. Otherwise, failing to account for the degree of paludification can lead to misleading forest productivity predictions and result in considerable overestimations of aboveground carbon stocks from trees in the boreal regions.
Early onset SARS-CoV-2 pneumonia in a preterm neonate – Probably acquired through vertical transmission
Authors: Kalane Shilpa , Gokhale Asha , Patwardhan Sampada 
Published: August 2020

Abstract
With the increasing number of published case reports and studies, probability of newborns acquiring COVID-19 infection through vertical transmission is on rise. Although the modes of transmission for neonatal COVID-19 infection are becoming clearer, the clinical spectrum in the form of radiology and laboratory parameters have still not been studied well. We report a case of a preterm neonate, whose mother had tested positive for COVID-19 infection before delivery. The neonate was asphyxiated and had meconium aspiration syndrome. RT-PCR of her endotracheal secretions for COVID-19 tested positive within 24 hours of life and at 72 hours. The laboratory investigations were suggestive of cytokine storm syndrome (CSS) and the CT scan chest supported the diagnosis of COVID-19 pneumonia. This is probably the youngest neonate with COVID-19 infection showing CSS.
Catestatin (Cst) protects the brain against ischemia/reperfusion injury through suppressing ER-stress and mitochondrial dysfunction
Authors: Bing Pei , Song Chunjie , Zhang Zhengjiang , Xin Shen , Qian Cui 
Published: August 2020

Abstract
BackgroundCerebral stroke, known as a cerebral vascular accident (CVA), is one of the leading causes of long-term disability and the second leading cause of death worldwide. Despite amounts of advances that have been achieved in terms of the treatment of ischemic stroke. But thus far, clinically effective neuroprotectants remain elusive, which may mainly due to the lack of a complete understanding of molecular mechanisms of the stroke. Previous studies have been revealed that catestatin (Cst) is closely related to cardiovascular ischemia/reperfusion injuries. However, little is known about whether Cst is involved in the regulation of neuronal death processes during ischemia. MethodsIn the present study, we revealed a protective function of Cst on Rat neuron cell death in the setting of ischemia/reperfusion injury. ResultsWe found that Cst treatment significantly attenuated the deficits of hippocampal related behaviors. On mechanism, our data revealed that Cst administration remarkably reduced ER-stress and mitochondrial dysfunction caused by I/R injury, and subsequently protected brain cells from apoptosis. ConclusionIn sum, our results demonstrate that Cst ameliorates I/R injury-induced hippocampal-related behaviors deficits by protecting the neurons from I/R injury-induced ER-stress and mitochondrial dysfunction and apoptosis. Our findings may provide a promising novel neuroprotectant for ischemic stroke therapy.
The Potential Role of Nrf2-PD-L1 Axis in Promoting of Oxaliplatin Resistance in Colon Cancer Cells
Authors: Payandeh Zahra , Tazehkand Abbas Pirpour , Mansoori Behzad , Khaze Vahid , Asadi Milad , Samadi Nasser , Baradaran Behzad 
Published: August 2020

Abstract
Background: Nuclear factor−erythroid 2−related factor 2 (Nrf2) has a key function in promoting chemoresistance in various cancers. PD-L1 is one of the downstream targets of Nrf2 signaling pathway, having some beneficial impacts on tumors growth by inhibition of the immune system. The aim of this study was to investigate the potential role of Nrf2- PD- L1 axis in the promotion of oxaliplatin resistance in colon cancer cells. Result: Our data revealed that Nrf2 and PD-L1 mRNA expressions were markedly higher in tumor tissues compared to margin tissues. PD-L1 mRNA expression level was also increased in the resistant cells. However, Nrf2 expression was decreased and increased in SW480/Res and LS174T/Res cells, respectively. Nrf2 inhibition through siRNA in SW480/Res and LS174T/Res decreased the IC50 values of oxaliplatin. Inhibition of Nrf2 significantly increased oxaliplatin-induced apoptosis and reduced migration in SW480/Res cells when accompanied with oxaliplatin. Conclusion: Our study suggests that effective inhibition of Nrf2/PD-L1 signaling pathways can be considered as a novel approach to improve oxaliplatin efficacy in colon cancer patients.
The Retrotransposition of L1 is Involved in the Reconsolidation of Contextual Fear Memory in Mice
Authors: Zhang Wen-Juan , Huang Yan-Qing , Fu Ao , Chen Kang-Zhi , Li Song-Ji , Zhang Qi , Zou Guang-Jing , Liu Yu , Su Jing-Zhi , Zhou Shi-Fen , Liu Jun-Wen , Li Fang , Bi Fang-Fang , Li Chang-Qi 
Published: August 2020

Background:
The long interspersed element-1 (L1) participates in memory formation,
and DNA methylation patterns of L1 may suggest resilience or vulnerability factors for Post-Traumatic
Stress Disorder (PTSD), of which the principal manifestation is a pathological exacerbation
of fear memory. However, the unique roles of L1 in the reconsolidation of fear memory remain
poorly understood.

Objective:
The study aimed to investigate the role of L1 in the reconsolidation of context-dependent
fear memory.

Methods:
Mice underwent fear conditioning and fear recall in the observation chambers. Fear memory
was assessed by calculating the percentage of time spent freezing in 5 min. The medial prefrontal
cortex (mPFC) and hippocampus were removed for further analysis. Open Reading Frame 1
(ORF1) mRNA and ORF2 mRNA of L1 were analyzed by real-time quantitative polymerase chain
reaction. After reactivation of fear memory, lamivudine was administered and its effects on fear memory
reconsolidation were observed.

Results:
ORF1 and ORF2 mRNA expressions in the mPFC and hippocampus after recent (24 h)
and remote (14 days) fear memory recall exhibited augmentation via different temporal and spatial
patterns. Reconsolidation of fear memory was markedly inhibited in mice treated with lamivudine,
which could block L1. DNA methyltransferase mRNA expression declined following lamivudine
treatment in remote fear memory recall.

Conclusions:
The retrotransposition of L1 participated in the reconsolidation of fear memory after
reactivation of fear memory, and with lamivudine treatment, spontaneous recovery decreased with
time after recent and remote fear memory recall, providing clues for understanding the roles of L1
in fear memory.
Securing Energy Routing Protocol Against Black Hole Attacks in Mobile
Ad-Hoc Network
Authors: P. Rajendra Prasad , Shankar Shiva 
Published: August 2020

Introduction:
The aim of securing energy routing protocol was to provide the countermeasures
to the attacks, particularly to the black hole in a mobile ad-hoc network, and enhancing
the network performance metric throughput, also reducing the end-to-end delay between the nodes
in the network. To build the protocol that enhances the performance of the network by modifying
the existing DSR protocol and by introducing a new route discovery mechanism in the proposed
protocol.

Methods:
The proposed protocol implementation has two phases, route request/reply phase and
route confirm phases. During the route discovery process, the route discovery from the source to the
destination process is described by sending the RREQ packet from the source hub, as shown in Fig.
1(a), when it does not have one accessible and cravings a route to a destination. The source node
transmits the RREQ to its associate nodes and the destination node reply with RREP. When the
source receives a reply message, the source node responds with a reverse path with a confirm
RCON message and providing security to the nodes in the network.

Results:
To verify the performance of the proposed protocol against the existing DSR protocol are
compared with respect to various network metrics like end-to-end delay and packet delivery ratio
and validated the result by comparing both routing algorithm using Network Simulator 2.

Conclusion:
The results of the proposed SERP strongly safeguard against the attacks in the network,
and the packet delivery ratio is increased compared with the DSR; also, the end-to-end delay
is reduced in the proposed protocol.

Discussion:
Mobile ad-hoc networks are being dynamic in nature; it associates with issues related
to secure routing, energy and are generally vulnerable to several types of attacks. The DSR is one of
the widely used reactive protocols available for the mobile ad-hoc network and the proposed work
enhancing the security of the network in the existing pro.
Pelembagaan Partai Politik: Studi Pada Partai Solidaritas Indonesia (PSI) Kota Bandung Tahun 2019
Authors: Suryana Nanang , Ardiansyah Ari Ganjar , Manan Firman 
Published: August 2020

Penelitian ini bertujuan menganalisis proses pelembagaan Partai Solidaritas Indonesia (PSI) Kota Bandung. Penelitian ini didesain dengan menggunakan metode kualitatif. Bertolak dari kerangka teoritik pelembagaan partai politik, penelitian ini menghasilkan beberapa temuan yang berfokus pada empat derajat pelembagaan. Hasil penelitian memperlihatkan derajat kesisteman (systemness) dalam proses pelembagaan di tubuh PSI Kota Bandung masih jauh dari kata ideal. Faktor-faktor seperti penggunaan aturan, prosedur, dan mekanisme yang disepakati dan ditetapkan dalam konstitusi partai belum mampu diterjemahkan PSI Kota Bandung dalam menajemen keorganisasian. Di level derajat identitas nilai (value infusion), PSI Kota Bandung konsisten mengusung nilai yang menjadi landasan partai. Namun, secara prakis beberapa narasi yang diusung partai tidak terlalu mendatangkan insentif secara elektoral. Di level decisional autonomy, kondisi PSI Kota Bandung yang hanya mengandalkan sumber pembiayaan partai dari sumber internal, kendati kondisi ini memberikan keleluasaan dan derajat otonomi suatu partai dalam pembuatan keputusan, namun keterbatasan kemampuan keuangan berdampak pada efektifitas jalannya organisasi. Di level value infusion, narasi dan isu yang dibawa parrtai menjadikan mereka dekat dengan segmen pemilih dari kelompok minoritas, baik dari kelompok keagamaan maupun etnis. Di level keempat (reification), diferensiasi identitas yang dibawa partai nampak belum membumi di tengah publik Kota Bandung.