bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lithium: a potential therapeutic strategy in obsessive–compulsive disorder by targeting the canonical WNT/β pathway
Authors: Vallée Alexandre , Vallée Jean-Noël , Lecarpentier Yves 
Published: April 2021

AbstractObsessive–compulsive disorder (OCD) is a neuropsychiatric disorder characterized b–y recurrent and distinctive obsessions and/or compulsions. The etiologies remain unclear. Recent findings have shown that oxidative stress, inflammation, and the glutamatergic pathway play key roles in the causes of OCD. However, first-line therapies include cognitive–behavioral therapy but only 40% of the patients respond to this first-line therapy. Research for a new treatment is mandatory. This review focuses on the potential effects of lithium, as a potential therapeutic strategy, on OCD and some of the presumed mechanisms by which lithium provides its benefit properties. Lithium medication downregulates GSK-3β, the main inhibitor of the WNT/β-catenin pathway. The activation of the WNT/β-catenin could be associated with the control of oxidative stress, inflammation, and glutamatergic pathway. Future prospective clinical trials could focus on lithium and its different and multiple interactions in OCD.
The effect of geriatric intervention in frail older patients receiving chemotherapy for colorectal cancer: a randomised trial (GERICO)
Authors: Lund Cecilia Margareta , Vistisen Kirsten Kjeldgaard , Olsen Anne Pries , Bardal Pernille , Schultz Martin , Dolin Troels Gammeltoft , Rønholt Finn , Johansen Julia Sidenius , Nielsen Dorte Lisbeth 
Published: April 2021

Abstract
Background
Older patients with colorectal cancer (CRC) experience chemotherapy dose reductions or discontinuation. Comprehensive geriatric assessment (CGA) predicts survival and chemotherapy completion in patients with cancer, but the benefit of geriatric interventions remains unexplored.

Methods
The GERICO study is a randomised Phase 3 trial including patients ≥70 years receiving adjuvant or first-line palliative chemotherapy for CRC. Vulnerable patients (G8 questionnaire ≤14 points) were randomised 1:1 to CGA-based interventions or standard care, along with guideline-based chemotherapy. The primary outcome was chemotherapy completion without dose reductions or delays. Secondary outcomes were toxicity, survival and quality of life (QoL).

Results
Of 142 patients, 58% received adjuvant and 42% received first-line palliative chemotherapy. Interventions included medication changes (62%), nutritional therapy (51%) and physiotherapy (39%). More interventional patients completed scheduled chemotherapy compared with controls (45% vs. 28%, P = 0.0366). Severe toxicity occurred in 39% of controls and 28% of interventional patients (P = 0.156). QoL improved in interventional patients compared with controls with the decreased burden of illness (P = 0.048) and improved mobility (P = 0.008).

Conclusion
Geriatric interventions compared with standard care increased the number of older, vulnerable patients with CRC completing adjuvant chemotherapy, and may improve the burden of illness and mobility.

Trial registration
ClinicalTrials.gov ID: NCT 02748811.
NDUFA4L2 promotes glioblastoma progression, is associated with poor survival, and can be effectively targeted by apatinib
Authors: Chen Zheng , Wei Xiangyu , Wang Xueyi , Zheng Xuan , Chang Bowen , Shen Lin , Zhu Hanshuo , Yang Min , Li Shiting , Zheng Xuesheng 
Published: April 2021

AbstractNADH dehydrogenase [ubiquinone] 1 alpha subcomplex, 4-like 2 (NDUFA4L2) is a subunit of Complex I of the mitochondrial respiratory chain, which is important in metabolic reprogramming and oxidative stress in multiple cancers. However, the biological role and molecular regulation of NDUFA4L2 in glioblastoma (GBM) are poorly understood. Here, we found that NDUFA4L2 was significantly upregulated in GBM; the elevated levels were correlated with reduced patient survival. Gene knockdown of NDUFA4L2 inhibited tumor cell proliferation and enhanced apoptosis, while tumor cells initiated protective mitophagy in vitro and in vivo. We used lentivirus to reduce expression levels of NDUFA4L2 protein in GBM cells exposed to mitophagy blockers, which led to a significant enhancement of tumor cell apoptosis in vitro and inhibited the development of xenografted tumors in vivo. In contrast to other tumor types, NDUFA4L2 expression in GBM may not be directly regulated by hypoxia-inducible factor (HIF)-1α, because HIF-1α inhibitors failed to inhibit NDUFA4L2 in GBM. Apatinib was able to effectively target NDUFA4L2 in GBM, presenting an alternative to the use of lentiviruses, which currently cannot be used in humans. Taken together, our data suggest the use of NDUFA4L2 as a potential therapeutic target in GBM and demonstrate a practical treatment approach.
Fangchinoline suppresses conjunctival melanoma by directly binding FUBP2 and inhibiting the homologous recombination pathway
Authors: Bao Keting , Li Yongyun , Wei Jinlian , Li Ruoxi , Yang Jie , Shi Jiahao , Li Baoli , Zhu Jin , Mao Fei , Jia Renbing , Li Jian 
Published: April 2021

AbstractConjunctival melanoma (CM) is a rare and fatal ocular tumour with poor prognosis. There is an urgent need of effective therapeutic drugs against CM. Here, we reported the discovery of a novel potential therapeutic target for CM. Through phenotypic screening of our in-house library, fangchinoline was discovered to significantly inhibit the growth of CM cells including CM-AS16, CRMM1, CRMM2 and CM2005.1. Further mechanistic experiments indicated that fangchinoline suppressed the homologous recombination (HR)-directed DNA repair by binding with far upstream element binding protein 2 (FUBP2) and downregulating the expression of HR factors BRCA1 and RAD51. In vitro and in vivo antitumour experiments revealed that fangchinoline increased the efficacy of cisplatin by blocking HR factors and reduced the drug dose and toxicity. In conclusion, our work provides a promising therapeutic strategy for the treatment of CM that is worthy of extensive preclinical investigation.
The chromosome-level Hemerocallis citrina Borani genome provides new insights into the rutin biosynthesis and the lack of colchicine
Authors: Qing Zhixing , Liu Jinghong , Yi Xinxin , Liu Xiubin , Hu Guoan , Lao Jia , He Wei , Yang Zihui , Zou Xiaoyan , Sun Mengshan , Huang Peng , Zeng Jianguo 
Published: April 2021

AbstractHemerocallis citrina Borani (huang hua cai in Chinese) is an important horticultural crop whose flower buds are widely consumed as a delicious vegetable in Asia. Here we assembled a high-quality reference genome of H. citrina using single-molecule sequencing and Hi-C technologies. The genome assembly was 3.77 Gb and consisted of 3183 contigs with a contig N50 of 2.09 Mb, which were further clustered into 11 pseudochromosomes. A larger portion (3.25 Gb or 86.20%) was annotated as a repetitive content and 54,295 protein-coding genes were annotated in the genome. Genome evolution analysis showed that H. citrina experienced a recent whole-genome duplication (WGD) event at ~15.73 million years ago (Mya), which was the main factor leading to many multiple copies of orthologous genes. We used this reference genome to predict 20 genes involved in the rutin biosynthesis pathway. Moreover, our metabolomics data revealed neither colchicine nor its precursors in H. citrina, challenging the long-standing belief that this alkaloid causes poisoning by the plant. The results of our disruptive research are further substantiated by our genomic finding that H. citrina does not contain any genes involved in colchicine biosynthesis. The high-quality genome lays a solid foundation for genetic research and molecular breeding of H. citrina.
VESPER: global and local cryo-EM map alignment using local density vectors
Authors: Han Xusi , Terashi Genki , Christoffer Charles , Chen Siyang , Kihara Daisuke 
Published: April 2021

AbstractAn increasing number of density maps of biological macromolecules have been determined by cryo-electron microscopy (cryo-EM) and stored in the public database, EMDB. To interpret the structural information contained in EM density maps, alignment of maps is an essential step for structure modeling, comparison of maps, and for database search. Here, we developed VESPER, which captures the similarity of underlying molecular structures embedded in density maps by taking local gradient directions into consideration. Compared to existing methods, VESPER achieved substantially more accurate global and local alignment of maps as well as database retrieval.
Cryo-EM structure of the human histamine H1 receptor/Gq complex
Authors: Xia Ruixue , Wang Na , Xu Zhenmei , Lu Yang , Song Jing , Zhang Anqi , Guo Changyou , He Yuanzheng 
Published: April 2021

AbstractHistamine receptors play important roles in various pathophysiological conditions and are effective targets for anti-allergy treatment, however the mechanism of receptor activation remain elusive. Here, we present the cryo-electron microscopy (cryo-EM) structure of the human H1R in complex with a Gq protein in an active conformation via a NanoBiT tethering strategy. The structure reveals that histamine activates receptor via interacting with the key residues of both transmembrane domain 3 (TM3) and TM6 to squash the binding pocket on the extracellular side and to open the cavity on the intracellular side for Gq engagement in a model of “squash to activate and expand to deactivate”. The structure also reveals features for Gq coupling, including the interaction between intracellular loop 2 (ICL2) and the αN-β junction of Gq/11 protein. The detailed analysis of our structure will provide a framework for understanding G-protein coupling selectivity and clues for designing novel antihistamines.
Intracellular trafficking of Notch orchestrates temporal dynamics of Notch activity in the fly brain
Authors: Wang Miaoxing , Han Xujun , Liu Chuyan , Takayama Rie , Yasugi Tetsuo , Ei Shin-Ichiro , Nagayama Masaharu , Tanaka Yoshitaro , Sato Makoto 
Published: April 2021

AbstractWhile Delta non-autonomously activates Notch in neighboring cells, it autonomously inactivates Notch through cis-inhibition, the molecular mechanism and biological roles of which remain elusive. The wave of differentiation in the Drosophila brain, the ‘proneural wave’, is an excellent model for studying Notch signaling in vivo. Here, we show that strong nonlinearity in cis-inhibition reproduces the second peak of Notch activity behind the proneural wave in silico. Based on this, we demonstrate that Delta expression induces a quick degradation of Notch in late endosomes and the formation of the twin peaks of Notch activity in vivo. Indeed, the amount of Notch is upregulated and the twin peaks are fused forming a single peak when the function of Delta or late endosomes is compromised. Additionally, we show that the second Notch peak behind the wavefront controls neurogenesis. Thus, intracellular trafficking of Notch orchestrates the temporal dynamics of Notch activity and the temporal patterning of neurogenesis.
The NIH Somatic Cell Genome Editing program
Authors:   The SCGE Consortium, Saha Krishanu , Sontheimer Erik J. , Brooks P. J. , Dwinell Melinda R. , Gersbach Charles A. , Liu David R. , Murray Stephen A. , Tsai Shengdar Q. , Wilson Ross C. , Anderson Daniel G. , Asokan Aravind , Banfield Jillian F. , Bankiewicz Krystof S. , Bao Gang , Bulte Jeff W. M. , Bursac Nenad , Campbell Jarryd M. , Carlson Daniel F. , Chaikof Elliot L. , Chen Zheng-Yi , Cheng R. Holland , Clark Karl J. , Curiel David T. , Dahlman James E. , Deverman Benjamin E. , Dickinson Mary E. , Doudna Jennifer A. , Ekker Stephen C. , Emborg Marina E. , Feng Guoping , Freedman Benjamin S. , Gamm David M. , Gao Guangping , Ghiran Ionita C. , Glazer Peter M. , Gong Shaoqin , Heaney Jason D. , Hennebold Jon D. , Hinson John T. , Khvorova Anastasia , Kiani Samira , Lagor William R. , Lam Kit S. , Leong Kam W. , Levine Jon E. , Lewis Jennifer A. , Lutz Cathleen M. , Ly Danith H. , Maragh Samantha , McCray Paul B. , McDevitt Todd C. , Mirochnitchenko Oleg , Morizane Ryuji , Murthy Niren , Prather Randall S. , Ronald John A. , Roy Subhojit , Roy Sushmita , Sabbisetti Venkata , Saltzman W. Mark , Santangelo Philip J. , Segal David J. , Shimoyama Mary , Skala Melissa C. , Tarantal Alice F. , Tilton John C. , Truskey George A. , Vandsburger Moriel , Watts Jonathan K. , Wells Kevin D. , Wolfe Scot A. , Xu Qiaobing , Xue Wen , Yi Guohua , Zhou Jiangbing 
Published: April 2021

AbstractThe move from reading to writing the human genome offers new opportunities to improve human health. The United States National Institutes of Health (NIH) Somatic Cell Genome Editing (SCGE) Consortium aims to accelerate the development of safer and more-effective methods to edit the genomes of disease-relevant somatic cells in patients, even in tissues that are difficult to reach. Here we discuss the consortium’s plans to develop and benchmark approaches to induce and measure genome modifications, and to define downstream functional consequences of genome editing within human cells. Central to this effort is a rigorous and innovative approach that requires validation of the technology through third-party testing in small and large animals. New genome editors, delivery technologies and methods for tracking edited cells in vivo, as well as newly developed animal models and human biological systems, will be assembled—along with validated datasets—into an SCGE Toolkit, which will be disseminated widely to the biomedical research community. We visualize this toolkit—and the knowledge generated by its applications—as a means to accelerate the clinical development of new therapies for a wide range of conditions.
Initial Upper Palaeolithic humans in Europe had recent Neanderthal ancestry
Authors: Hajdinjak Mateja , Mafessoni Fabrizio , Skov Laurits , Vernot Benjamin , Hübner Alexander , Fu Qiaomei , Essel Elena , Nagel Sarah , Nickel Birgit , Richter Julia , Moldovan Oana Teodora , Constantin Silviu , Endarova Elena , Zahariev Nikolay , Spasov Rosen , Welker Frido , Smith Geoff M. , Sinet-Mathiot Virginie , Paskulin Lindsey , Fewlass Helen , Talamo Sahra , Rezek Zeljko , Sirakova Svoboda , Sirakov Nikolay , McPherron Shannon P. , Tsanova Tsenka , Hublin Jean-Jacques , Peter Benjamin M. , Meyer Matthias , Skoglund Pontus , Kelso Janet , Pääbo Svante 
Published: April 2021

AbstractModern humans appeared in Europe by at least 45,000 years ago1–5, but the extent of their interactions with Neanderthals, who disappeared by about 40,000 years ago6, and their relationship to the broader expansion of modern humans outside Africa are poorly understood. Here we present genome-wide data from three individuals dated to between 45,930 and 42,580 years ago from Bacho Kiro Cave, Bulgaria1,2. They are the earliest Late Pleistocene modern humans known to have been recovered in Europe so far, and were found in association with an Initial Upper Palaeolithic artefact assemblage. Unlike two previously studied individuals of similar ages from Romania7 and Siberia8 who did not contribute detectably to later populations, these individuals are more closely related to present-day and ancient populations in East Asia and the Americas than to later west Eurasian populations. This indicates that they belonged to a modern human migration into Europe that was not previously known from the genetic record, and provides evidence that there was at least some continuity between the earliest modern humans in Europe and later people in Eurasia. Moreover, we find that all three individuals had Neanderthal ancestors a few generations back in their family history, confirming that the first European modern humans mixed with Neanderthals and suggesting that such mixing could have been common.
Assessment of tumor hypoxia and perfusion in recurrent glioblastoma following bevacizumab failure using MRI and 18F-FMISO PET
Authors: Huang Shiliang , Michalek Joel E. , Reardon David A. , Wen Patrick Y. , Floyd John R. , Fox Peter T. , Clarke Geoffrey D. , Jerabek Paul A. , Schmainda Kathleen M. , Muzi Mark , Hyun Hyewon , Lee Eudocia Quant , Brenner Andrew J. 
Published: April 2021

AbstractTumoral hypoxia correlates with worse outcomes in glioblastoma (GBM). While bevacizumab is routinely used to treat recurrent GBM, it may exacerbate hypoxia. Evofosfamide is a hypoxia-targeting prodrug being tested for recurrent GBM. To characterize resistance to bevacizumab and identify those with recurrent GBM who may benefit from evofosfamide, we ascertained MRI features and hypoxia in patients with GBM progression receiving both agents. Thirty-three patients with recurrent GBM refractory to bevacizumab were enrolled. Patients underwent MR and 18F-FMISO PET imaging at baseline and 28 days. Tumor volumes were determined, MRI and 18F-FMISO PET-derived parameters calculated, and Spearman correlations between parameters assessed. Progression-free survival decreased significantly with hypoxic volume [hazard ratio (HR) = 1.67, 95% confidence interval (CI) 1.14 to 2.46, P = 0.009] and increased significantly with time to the maximum value of the residue (Tmax) (HR = 0.54, 95% CI 0.34 to 0.88, P = 0.01). Overall survival decreased significantly with hypoxic volume (HR = 1.71, 95% CI 1.12 to 12.61, p = 0.01), standardized relative cerebral blood volume (srCBV) (HR = 1.61, 95% CI 1.09 to 2.38, p = 0.02), and increased significantly with Tmax (HR = 0.31, 95% CI 0.15 to 0.62, p < 0.001). Decreases in hypoxic volume correlated with longer overall and progression-free survival, and increases correlated with shorter overall and progression-free survival. Hypoxic volume and volume ratio were positively correlated (rs = 0.77, P < 0.0001), as were hypoxia volume and T1 enhancing tumor volume (rs = 0.75, P < 0.0001). Hypoxia is a key biomarker in patients with bevacizumab-refractory GBM. Hypoxia and srCBV were inversely correlated with patient outcomes. These radiographic features may be useful in evaluating treatment and guiding treatment considerations.
Phylogeography and morphological evolution of Pseudechiniscus (Heterotardigrada: Echiniscidae)
Authors: Gąsiorek Piotr , Vončina Katarzyna , Zając Krzysztof , Michalczyk Łukasz 
Published: April 2021

AbstractTardigrades constitute a micrometazoan phylum usually considered as taxonomically challenging and therefore difficult for biogeographic analyses. The genus Pseudechiniscus, the second most speciose member of the family Echiniscidae, is commonly regarded as a particularly difficult taxon for studying due to its rarity and homogenous sculpturing of the dorsal plates. Recently, wide geographic ranges for some representatives of this genus and a new hypothesis on the subgeneric classification have been suggested. In order to test these hypotheses, we sequenced 65 Pseudechiniscus populations extracted from samples collected in 19 countries distributed on 5 continents, representing the Neotropical, Afrotropical, Holarctic, and Oriental realms. The deep subdivision of the genus into the cosmopolitan suillus-facettalis clade and the mostly tropical-Gondwanan novaezeelandiae clade is demonstrated. Meridioniscus subgen. nov. is erected to accommodate the species belonging to the novaezeelandiae lineage characterised by dactyloid cephalic papillae that are typical for the great majority of echiniscids (in contrast to pseudohemispherical papillae in the suillus-facettalis clade, corresponding to the subgenus Pseudechiniscus). Moreover, the evolution of morphological traits (striae between dorsal pillars, projections on the pseudosegmental plate IV’, ventral sculpturing pattern) crucial in the Pseudechiniscus taxonomy is reconstructed. Furthermore, broad distributions are emphasised as characteristic of some taxa. Finally, the Malay Archipelago and Indochina are argued to be the place of origin and extensive radiation of Pseudechiniscus.
Drastic improvement of Curie temperature by chemical pressure in N-type diluted magnetic semiconductor Ba(Zn,Co)$$_{2}$$As$$_{2}$$
Authors: Fu Licheng , Gu Yilun , Zhi Guoxiang , Zhang Haojie , Zhang Rufei , Dong Jinou , Zhao Xueqin , Xie Lingfeng , Ning Fanlong 
Published: April 2021

AbstractWe report the effect of chemical pressure on the ferromagnetic ordering of the recently reported n-type diluted magnetic semiconductor Ba(Zn$$_{1-x}$$

1
-
x

Co$$_{x}$$

x

)$$_{2}$$

2

As$$_{2}$$

2

which has a maximum $$T_C$$

T
C

$$\sim$$
∼
45 K. Doping Sb into As-site and Sr into Ba-site induces negative and positive chemical pressure, respectively. While conserving the tetragonal crystal structure and n-type carriers, the unit cell volume shrink by $$\sim$$
∼
0.3$$\%$$
%
with 15$$\%$$
%
Sr doping, but drastically increase the ferromagnetic transition temperature by 18$$\%$$
%
to 53 K. Our experiment unequivocally demonstrate that the parameters of Zn(Co)As$$_{4}$$

4

tetrahedra play a vital role in the formation of ferromagnetic ordering in the Ba(Zn,Co)$$_{2}$$

2

As$$_{2}$$

2

DMS.
Cooperation in spatial public good games depends on the locality effects of game, adaptation, and punishment
Authors: Okada Isamu , Yamamoto Hitoshi , Akiyama Eizo , Toriumi Fujio 
Published: April 2021

AbstractDespite intensive studies on the evolution of cooperation in spatial public goods games, there have been few investigations into locality effects in interaction games, adaptation, and punishment. Here we analyze locality effects using an agent-based model of a regular graph. Our simulation shows that a situation containing a local game, local punishment, and global adaptation leads to the most robustly cooperative regime. Further, we show an interesting feature in local punishment. Previous studies showed that a local game and global adaptation are likely to generate cooperation. However, they did not consider punishment. We show that if local punishment is introduced in spatial public goods games, a situation satisfying either local game or local adaptation is likely to generate cooperation. We thus propose two principles. One is if interactions in games can be restricted locally, it is likely to generate cooperation independent of the interaction situations on punishment and adaptation. The other is if the games must be played globally, a cooperative regime requires both local punishment and local adaptation.
Methods for tuning plasmonic and photonic optical resonances in high surface area porous electrodes
Authors: Otto Lauren M. , Gaulding E. Ashley , Chen Christopher T. , Kuykendall Tevye R. , Hammack Aeron T. , Toma Francesca M. , Ogletree D. Frank , Aloni Shaul , Stadler Bethanie J. H. , Schwartzberg Adam M. 
Published: April 2021

AbstractSurface plasmons have found a wide range of applications in plasmonic and nanophotonic devices. The combination of plasmonics with three-dimensional photonic crystals has enormous potential for the efficient localization of light in high surface area photoelectrodes. However, the metals traditionally used for plasmonics are difficult to form into three-dimensional periodic structures and have limited optical penetration depth at operational frequencies, which limits their use in nanofabricated photonic crystal devices. The recent decade has seen an expansion of the plasmonic material portfolio into conducting ceramics, driven by their potential for improved stability, and their conformal growth via atomic layer deposition has been established. In this work, we have created three-dimensional photonic crystals with an ultrathin plasmonic titanium nitride coating that preserves photonic activity. Plasmonic titanium nitride enhances optical fields within the photonic electrode while maintaining sufficient light penetration. Additionally, we show that post-growth annealing can tune the plasmonic resonance of titanium nitride to overlap with the photonic resonance, potentially enabling coupled-phenomena applications for these three-dimensional nanophotonic systems. Through characterization of the tuning knobs of bead size, deposition temperature and cycle count, and annealing conditions, we can create an electrically- and plasmonically-active photonic crystal as-desired for a particular application of choice.