bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinico-genetic findings in 509 frontotemporal dementia patients
Authors: Wagner Matias , Lorenz Georg , Volk Alexander E. , Brunet Theresa , Edbauer Dieter , Berutti Riccardo , Zhao Chen , Anderl-Straub Sarah , Bertram Lars , Danek Adrian , Deschauer Marcus , Dill Veronika , Fassbender Klaus , Fliessbach Klaus , Götze Katharina S. , Jahn Holger , Kornhuber Johannes , Landwehrmeyer Bernhard , Lauer Martin , Obrig Hellmuth , Prudlo Johannes , Schneider Anja , Schroeter Matthias L. , Uttner Ingo , Vukovich Ruth , Wiltfang Jens , Winkler Andrea S. , Zhou Qihui , Ludolph Albert C. ,   The German FTLD consortium, Oexle Konrad , Otto Markus , Diehl-Schmid Janine , Winkelmann Juliane 
Published: October 2021

AbstractFrontotemporal dementia (FTD) is a clinically and genetically heterogeneous disorder. To which extent genetic aberrations dictate clinical presentation remains elusive. We investigated the spectrum of genetic causes and assessed the genotype-driven differences in biomarker profiles, disease severity and clinical manifestation by recruiting 509 FTD patients from different centers of the German FTLD consortium where individuals were clinically assessed including biomarker analysis. Exome sequencing as well as C9orf72 repeat analysis were performed in all patients. These genetic analyses resulted in a diagnostic yield of 18.1%. Pathogenic variants in C9orf72 (n = 47), GRN (n = 26), MAPT (n = 11), TBK1 (n = 5), FUS (n = 1), TARDBP (n = 1), and CTSF (n = 1) were identified across all clinical subtypes of FTD. TBK1-associated FTD was frequent accounting for 5.4% of solved cases. Detection of a homozygous missense variant verified CTSF as an FTD gene. ABCA7 was identified as a candidate gene for monogenic FTD. The distribution of APOE alleles did not differ significantly between FTD patients and the average population. Male sex was weakly associated with clinical manifestation of the behavioral variant of FTD. Age of onset was lowest in MAPT patients. Further, high CSF neurofilament light chain levels were found to be related to GRN-associated FTD. Our study provides large-scale retrospective clinico-genetic data such as on disease manifestation and progression of FTD. These data will be relevant for counseling patients and their families.
Astrocytes in the ventral pallidum extinguish heroin seeking through GAT-3 upregulation and morphological plasticity at D1-MSN terminals
Authors: Kruyer Anna , Dixon Danielle , Angelis Ariana , Amato Davide , Kalivas Peter W. 
Published: October 2021

AbstractGABAergic projections from the nucleus accumbens core to the dorsolateral ventral pallidum are necessary for drug-conditioned cues to initiate relapse-like drug seeking. Astrocytes in the ventral pallidum are situated perisynaptically and regulate GABA transmission through expression of GABA uptake transporters, but whether they are involved in regulating drug seeking is unknown. To determine the contribution of ventral pallidal astrocytes to heroin seeking, we labeled astrocytes in male and female rats with a membrane-bound fluorescent tag and used confocal microscopy to quantify astroglial expression of the GABA transporter GAT-3 and astrocyte synaptic proximity after withdrawal from heroin self-administration and during 15 min of cued heroin seeking. We found that GAT-3 was upregulated in rats that had extinguished heroin seeking, but not in animals that were withdrawn from heroin without extinction training or in rats that extinguished sucrose seeking. When GAT-3 upregulation was reversed using a vivo-morpholino oligo, heroin seeking was restored in the extinguished context and extinction of cued heroin seeking was disrupted compared to control animals. Although astrocyte synaptic proximity was not altered overall after heroin withdrawal, examination of astrocyte proximity to accumbens D1- or D2-expressing afferents revealed a selective increase in astrocyte proximity with D1-expressing terminals during extinction of heroin self-administration. Experimentally-induced reduction of astrocyte synaptic proximity through knockdown of the astrocyte-selective actin-binding protein ezrin also markedly disrupted extinction of heroin seeking. Notably, GAT-3 or ezrin knockdown had no impact on context- or cue-induced seeking in sucrose-trained animals. These data show that astrocytes in the ventral pallidum undergo plasticity after extinction of heroin use that reduces seeking and highlight the importance of astrocyte-neuron interactions in shaping behaviors associated with opioid use disorder.
Pharmacological treatment for bipolar mania: a systematic review and network meta-analysis of double-blind randomized controlled trials
Authors: Kishi Taro , Ikuta Toshikazu , Matsuda Yuki , Sakuma Kenji , Okuya Makoto , Nomura Ikuo , Hatano Masakazu , Iwata Nakao 
Published: October 2021

AbstractA systematic review and random-effects model network meta-analysis was conducted to compare the efficacy, acceptability, tolerability, and safety of pharmacological interventions for adults with acute bipolar mania. We searched PubMed, the Cochrane Library, and Embase databases for eligible studies published before March 14, 2021. Randomized controlled trials (RCTs) of oral medication monotherapy lasting ≥10 days in adults with mania were included, and studies that allowed the use of antipsychotics as a rescue medication during a trial were excluded. The primary outcomes were response to treatment (efficacy) and all-cause discontinuation (acceptability). The secondary outcomes were the improvement of mania symptoms and discontinuation due to inefficacy. Of the 79 eligible RCTs, 72 double-blind RCTs of 23 drugs and a placebo were included in the meta-analysis (mean study duration = 3.96 ± 2.39 weeks,n = 16442, mean age = 39.55 years, with 50.93% males). Compared with the placebo, aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperidone, quetiapine, risperidone, tamoxifen, valproate, and ziprasidone outperformed response to treatment (N = 56,n = 14503); aripiprazole, olanzapine, quetiapine, and risperidone had lower all-cause discontinuation; however, topiramate had higher all-cause discontinuation (N = 70,n = 16324). Compared with the placebo, aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperidone, quetiapine, risperidone, tamoxifen, valproate, and ziprasidone outperformed the improvement of mania symptoms (N = 61,n = 15466), and aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperidone, quetiapine, risperidone, valproate, and ziprasidone had lower discontinuation due to inefficacy (N = 50,n = 14284). In conclusions, these antipsychotics, carbamazepine, lithium, tamoxifen, and valproate were effective for acute mania. However, only aripiprazole, olanzapine, quetiapine, and risperidone had better acceptability than the placebo.
LncRNA RP11-465B22.8 triggers esophageal cancer progression by targeting miR-765/KLK4 axis
Authors: Hu Rui , Bi Rui , Jiang Lianyong , Xiao Haibo , Xie Xiao , Liu Hongtao , Hu Fengqing 
Published: October 2021

AbstractLncRNAs play an important role in tumorigenesis and progression; however, the function and mechanisms of lncRNAs in esophageal cancer (EC) remain largely unclear. In this study, we screened the differentially expressed lncRNAs in EC by using RNA-seq and one of the most upregulated lncRNAs, lncRNA RP11-465B22.8, was further characterized. LncRNA RP11-465B22.8 was upregulated in EC tissues and high lncRNA RP11-465B22.8 expression was associated with poor survival of EC patients. Ectopic expression of lncRNA RP11-465B22.8 enhanced the proliferation, migration, and invasion of EC cells, whereas knockdown of lncRNA RP11-465B22.8 led to the opposite effects. Mechanistically, lncRNA RP11-465B22.8 sponged miR-765 to increase the expression of KLK4. Moreover, LncRNA RP11-465B22.8 could be delivered from EC cells to macrophages via exosomes and subsequently induced M2 macrophage-induced cell migration and invasion. Our findings revealed a novel lncRNA RP11-465B22.8/miR-765/KLK4 pathway in EC and indicated that lncRNA RP11-465B22.8 might be a potential target for EC therapy.
Phosphorylated α-synuclein aggregated in Schwann cells exacerbates peripheral neuroinflammation and nerve dysfunction in Parkinson’s disease through TLR2/NF-κB pathway
Authors: Sun Li , Jiang Wen-Wen , Wang Ye , Yuan Yong-Sheng , Rong Zhe , Wu Jing , Fan Yi , Lu Ming , Zhang Ke-Zhong 
Published: October 2021

AbstractTo investigate the mechanism of peripheral neuropathy in Parkinson’s disease (PD), we prepared a PD mice model by long-term exposure of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to mimic PD pathology in humans and the sciatic nerves were taken for further research. It turned out that phosphorylated α-synuclein (p-α-syn) was significantly deposited in Schwann cells (SCs) of sciatic nerves possibly contributing to degenerated myelin SCs and atrophied axons in MPTP group. Further analysis confirmed that toll-like receptors (TLRs) were implicated with PD peripheral neuropathy, in which TLR2 exhibits the predominant expression. Increased expression of inflammatory factors about TLR2/nuclear factor kappa-B (NF-κB) pathway was noted in MPTP group compared to saline group, with proteins on other pathways showing no changes. Moreover, MPTP-challenged mice exhibited worse motor ability and damaged nerve conduction, implicating that p-α-syn neurotoxicity might be relevant to impairments of motor and sensory nerves. After the treatment of CU-CPT22, a TLR2 antagonist, p-α-syn accumulation, motor and sensory function were ameliorated in CU-CPT22 combined with MPTP group. Thus, we demonstrated that pathological p-α-syn might combine TLR2 to affect SCs activation, inflammatory response as well as motor and sensory function through TLR2/nuclear factor kappa-B (NF-κB) signaling pathway. This study firstly demonstrates a novel mechanism of p-α-syn accumulated in SCs of peripheral nerves, which extends our understanding on SCs-mediated peripheral neuroinflammation related to TLR2/NF-κB signaling pathway and sheds light on potential new therapeutic avenues for PD.
Interaction between CD36 and FABP4 modulates adipocyte-induced fatty acid import and metabolism in breast cancer
Authors: Gyamfi Jones , Yeo Joo Hye , Kwon Doru , Min Byung Soh , Cha Yoon Jin , Koo Ja Seung , Jeong Joon , Lee Jinu , Choi Junjeong 
Published: October 2021

AbstractAdipocytes influence breast cancer behaviour via fatty acid release into the tumour microenvironment. Co-culturing human adipocytes and breast cancer cells increased CD36 expression, with fatty acid import into breast cancer cells. Genetic ablation of CD36 attenuates adipocyte-induced epithelial-mesenchymal transition (EMT) and stemness. We show a feedforward loop between CD36 and STAT3; where CD36 activates STAT3 signalling and STAT3 binds to the CD36 promoter, regulating its expression. CD36 expression results in metabolic reprogramming, with a shift towards fatty acid oxidation. CD36 inhibition induces de novo lipogenesis in breast cancer cells. Increased CD36 expression occurs with increased FABP4 expression. We showed that CD36 directly interacts with FABP4 to regulate fatty acid import, transport, and metabolism. CD36 and FABP4 inhibition induces apoptosis in tumour cells. These results indicate that CD36 mediates fatty acid import from adipocytes into cancer cells and activates signalling pathways that drive tumour progression. Targeting CD36 may have a potential for therapy, which will target the tumour microenvironment.
Evolution of HER2-low expression from primary to recurrent breast cancer
Authors: Miglietta Federica , Griguolo Gaia , Bottosso Michele , Giarratano Tommaso , Lo Mele Marcello , Fassan Matteo , Cacciatore Matilde , Genovesi Elisa , De Bartolo Debora , Vernaci Grazia , Amato Ottavia , Conte PierFranco , Guarneri Valentina , Dieci Maria Vittoria 
Published: October 2021

AbstractAbout a half of HER2-negative breast cancer (BC) show HER2-low expression that can be targeted by new antibody-drug conjugates. The main aim of this study is to describe the evolution of HER2 expression from primary BC to relapse by including HER2-low category in both primary and recurrent BC samples. Patients with matched primary and relapse BC samples were included. HER2 was evaluated according to ASCO/CAP recommendations in place at the time of diagnosis. A cutoff of >10% cells staining for HER2-positivity was applied. HER2-negative cases were sub-classified as HER2-low (IHC = 1 + /2+ and ISH not amplified), or HER2-0 (IHC-0). 547 patients were included. The proportion of HER2-low cases was 34.2% on the primary tumor and 37.3% on the relapse samples. Among HER2-negative cases, HER2-low status was more frequent in HR-positive vs triple-negative tumors (47.3% vs 35.4% on primary tumor samples, 53.8% vs 36.2% on relapse samples). The overall rate of HER2 discordance was 38.0%, mostly represented by HER2-0 switching to HER2-low (15%) and HER2-low switching to HER2-0 (14%). Among patients with a primary HER2-negative tumor, the rate of HER2 discordance was higher in HR-positive/HER2-negative vs triple-negative cases (45.5% vs 36.7% p = 0.170). This difference was mostly driven by cases switching from HER2-0 to HER2-low. HER2-low expression is highly unstable during disease evolution. Relapse biopsy in case of a primary HER2-0 tumor may open new therapeutic opportunities in a relevant proportion of patients.
Hydrogel-based flexible materials for diabetes diagnosis, treatment, and management
Authors: Song Jiang , Zhang Yanni , Chan Siew Yin , Du Zhaoyi , Yan Yinjia , Wang Tengjiao , Li Peng , Huang Wei 
Published: October 2021

AbstractDiabetes is a chronic metabolic disease characterized by high glucose concentration in blood. Conventional management of diabetes requires skin pricking and subcutaneous injection, causing physical pain and physiological issues to diabetic individuals. Hydrogels possess unique advantages such as lightweight, stretchability, biocompatibility, and biodegradability, offering the opportunities to be integrated as flexible devices for diabetes management. This review highlights the development of hydrogels as flexible materials for diabetes applications in glucose monitoring, insulin delivery, wound care, and cell transplantation in recent years. Challenges and prospects in the development of hydrogel-based flexible devices for personalized management of diabetes are discussed as well.
Optimising classification of Parkinson’s disease based on motor, olfactory, neuropsychiatric and sleep features
Authors: Bestwick Jonathan P. , Auger Stephen D. , Schrag Anette E. , Grosset Donald G. , Kanavou Sofia , Giovannoni Gavin , Lees Andrew J. , Cuzick Jack , Noyce Alastair J. 
Published: October 2021

AbstractOlfactory loss, motor impairment, anxiety/depression, and REM-sleep behaviour disorder (RBD) are prodromal Parkinson’s disease (PD) features. PD risk prediction models typically dichotomize test results and apply likelihood ratios (LRs) to scores above and below cut-offs. We investigate whether LRs for specific test values could enhance classification between PD and controls. PD patient data on smell (UPSIT), possible RBD (RBD Screening Questionnaire), and anxiety/depression (LADS) were taken from the Tracking Parkinson’s study (n = 1046). For motor impairment (BRAIN test) in PD cases, published data were supplemented (n = 87). Control data (HADS for anxiety/depression) were taken from the PREDICT-PD pilot study (n = 1314). UPSIT, RBDSQ, and anxiety/depression data were analysed using logistic regression to determine which items were associated with PD. Gaussian distributions were fitted to BRAIN test scores. LRs were calculated from logistic regression models or score distributions. False-positive rates (FPRs) for specified detection rates (DRs) were calculated. Sixteen odours were associated with PD; LRs for this set ranged from 0.005 to 5511. Six RBDSQ and seven anxiety/depression questions were associated with PD; LRs ranged from 0.35 to 69 and from 0.002 to 402, respectively. BRAIN test LRs ranged from 0.16 to 1311. For a 70% DR, the FPR was 2.4% for the 16 odours, 4.6% for anxiety/depression, 16.0% for the BRAIN test, and 20.0% for the RBDSQ. Specific selections of (prodromal) PD marker features rather than dichotomized marker test results optimize PD classification. Such optimized classification models could improve the ability of algorithms to detect prodromal PD; however, prospective studies are needed to investigate their value for PD-prediction models.
A cognitive fingerprint in human random number generation
Authors: Schulz Marc-André , Baier Sebastian , Timmermann Benjamin , Bzdok Danilo , Witt Karsten 
Published: October 2021

AbstractIs the cognitive process of random number generation implemented via person-specific strategies corresponding to highly individual random generation behaviour? We examined random number sequences of 115 healthy participants and developed a method to quantify the similarity between two number sequences on the basis of Damerau and Levenshtein’s edit distance. “Same-author” and “different author” sequence pairs could be distinguished (96.5% AUC) based on 300 pseudo-random digits alone. We show that this phenomenon is driven by individual preference and inhibition of patterns and stays constant over a period of 1 week, forming a cognitive fingerprint.
Deploying and scaling distributed parallel deep neural networks on the Tianhe-3 prototype system
Authors: Wei Jia , Zhang Xingjun , Ji Zeyu , Li Jingbo , Wei Zheng 
Published: October 2021

AbstractDue to the increase in computing power, it is possible to improve the feature extraction and data fitting capabilities of DNN networks by increasing their depth and model complexity. However, the big data and complex models greatly increase the training overhead of DNN, so accelerating their training process becomes a key task. The Tianhe-3 peak speed is designed to target E-class, and the huge computing power provides a potential opportunity for DNN training. We implement and extend LeNet, AlexNet, VGG, and ResNet model training for a single MT-2000+ and FT-2000+ compute nodes, as well as extended multi-node clusters, and propose an improved gradient synchronization process for Dynamic Allreduce communication optimization strategy for the gradient synchronization process base on the ARM architecture features of the Tianhe-3 prototype, providing experimental data and theoretical basis for further enhancing and improving the performance of the Tianhe-3 prototype in large-scale distributed training of neural networks.
Production of valuable chemicals from glycerol using carbon fiber catalysts derived from ethylene
Authors: Malaika Anna , Ptaszyńska Karolina , Kozłowski Mieczysław 
Published: October 2021

AbstractEthylene was thermocatalytically transformed into carbon products via a CCVD process. The filamentous carbon obtained was further modified with concentrated sulfuric acid or 4‐benzenediazonium sulfonate (BDS) to produce acid-type catalysts. The as-prepared samples were characterized by SEM and TEM techniques to confirm their morphological features. TG, XRD, elemental, and porosity analyses were also performed to assess the quality of these materials. The fabricated carbons were tested in eco-friendly green synthesis of value-added fuel bio-additives, namely in glycerol esterification. The reaction of glycerol transformation was performed with acetic acid at 80 °C using different glycerol to acetic acid (Gly/AA) molar ratios. The samples functionalized with diazonium salt showed better performance in the above process than those modified with H2SO4, and this was found to be directly related to the degree of surface functionalization with acidic sites. BDS-modified carbon fibers allowed obtaining acceptable results within 6 h when the reaction was performed with a Gly/AA molar ratio of 1:6, however, the dominant products in this case were mono- and diacetins. Extended reaction time altered the distribution of products. Finally, the combined selectivity to the targeted acetins (i.e., DA and TA) was about 75.5%. A direct correlation between the content of –SO3H groups of CNFs and the yield of higher acetins was found.
Major pulmonary resection after neoadjuvant chemotherapy or chemoradiation in potentially resectable stage III non-small cell lung carcinoma
Authors: Peer Michael , Azzam Sharbel , Cyjon Arnold , Katsnelson Rivka , Hayat Henri , Bar Ilan , Merimsky Ofer 
Published: October 2021

AbstractThe aim of this study was to identify predictors of postoperative outcome and survival of locally advanced non-small cell lung carcinoma (NSCLC) resections after neoadjuvant chemotherapy or chemoradiation. Medical records of all patients with clinical stage III potentially resectable NSCLC initially treated by neoadjuvant chemotherapy or chemoradiation followed by major pulmonary resections were retrieved from the databases of four Israeli Medical Centers between 1999 to 2019. The 124 suitable patients included, 86 males (69.4%) and 38 females (30.6%), with an average age of 64.2 years (range 37–82) and an average hospital stay of 12.6 days (range 5–123). Complete resection was achieved in 92.7% of the patients, while complete pathologic response was achieved in 35.5%. The overall readmission rate was 16.1%. The overall 5-year survival rate was 47.9%. One patient (0.8%) had local recurrence. Postoperative complications were reported in 49.2% of the patients, mainly atrial fibrillation (15.9%) and pneumonia (13.7%), empyema (10.3%), and early bronchopleural fistula (7.3%). The early in-hospital mortality rate was 6.5%, and the 6-month mortality rate was 5.6%. Pre-neoadjuvant bulky mediastinal disease (lymph nodes > 20 mm) (p = 0.034), persistent postoperative N2 disease (p = 0.016), R1 resection (p = 0.027), preoperative N2 multistation disease (p = 0.053) and postoperative stage IIIA (p = 0.001) emerged as negative predictive factors for survival. Our findings demonstrate that neoadjuvant chemotherapy or chemoradiation in locally advanced potentially resectable NSCLC, followed by major pulmonary resection, is a beneficial approach in selected cases.
Machine learning enabling prediction of the bond dissociation enthalpy of hypervalent iodine from SMILES
Authors: Nakajima Masaya , Nemoto Tetsuhiro 
Published: October 2021

AbstractMachine learning to create models on the basis of big data enables predictions from new input data. Many tasks formerly performed by humans can now be achieved by machine learning algorithms in various fields, including scientific areas. Hypervalent iodine compounds (HVIs) have long been applied as useful reactive molecules. The bond dissociation enthalpy (BDE) value is an important indicator of reactivity and stability. Experimentally measuring the BDE value of HVIs is difficult, however, and the value has been estimated by quantum calculations, especially density functional theory (DFT) calculations. Although DFT calculations can access the BDE value with high accuracy, the process is highly time-consuming. Thus, we aimed to reduce the time for predicting the BDE by applying machine learning. We calculated the BDE of more than 1000 HVIs using DFT calculations, and performed machine learning. Converting SMILES strings to Avalon fingerprints and learning using a traditional Elastic Net made it possible to predict the BDE value with high accuracy. Furthermore, an applicability domain search revealed that the learning model could accurately predict the BDE even for uncovered inputs that were not completely included in the training data.