bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dual network analysis of transcriptome data for discovery of new therapeutic targets in non-small cell lung cancer
Authors: Bai Yuquan , Zhou Lu , Zhang Chuanfen , Guo Minzhang , Xia Liang , Tang Zhenying , Liu Yi , Deng Senyi 
Published: October 2023

AbstractThe drug therapy for non-small cell lung cancer (NSCLC) have always been issues of poisonous side effect, acquired drug resistance and narrow applicable population. In this study, we built a novel network analysis method (difference- correlation- enrichment- causality- node), which was based on the difference analysis, Spearman correlation network analysis, biological function analysis and Bayesian causality network analysis to discover new therapeutic target of NSCLC in the sequencing data of BEAS-2B and 7 NSCLC cell lines. Our results showed that, as a proteasome subunit coding gene in the central of cell cycle network, PSMD2 was associated with prognosis and was an independent prognostic factor for NSCLC patients. Knockout of PSMD2 inhibited the proliferation of NSCLC cells by inducing cell cycle arrest, and exhibited marked increase of cell cycle blocking protein p21, p27 and decrease of cell cycle driven protein CDK4, CDK6, CCND1 and CCNE1. IPA and molecular docking suggested bortezomib has stronger affinity to PSMD2 compared with reported targets PSMB1 and PSMB5. In vitro and In vivo experiments demonstrated the inhibitory effect of bortezomib in NSCLC with different driven mutations or with tyrosine kinase inhibitors resistance. Taken together, bortezomib could target PSMD2, PSMB1 and PSMB5 to inhibit the proteasome degradation of cell cycle check points, to block cell proliferation of NSCLC, which was potential optional drug for NSCLC patients.
From signalling pathways to targeted therapies: unravelling glioblastoma’s secrets and harnessing two decades of progress
Authors: Dewdney Brittany , Jenkins Misty R. , Best Sarah A. , Freytag Saskia , Prasad Krishneel , Holst Jeff , Endersby Raelene , Johns Terrance G. 
Published: October 2023

AbstractGlioblastoma, a rare, and highly lethal form of brain cancer, poses significant challenges in terms of therapeutic resistance, and poor survival rates for both adult and paediatric patients alike. Despite advancements in brain cancer research driven by a technological revolution, translating our understanding of glioblastoma pathogenesis into improved clinical outcomes remains a critical unmet need. This review emphasises the intricate role of receptor tyrosine kinase signalling pathways, epigenetic mechanisms, and metabolic functions in glioblastoma tumourigenesis and therapeutic resistance. We also discuss the extensive efforts over the past two decades that have explored targeted therapies against these pathways. Emerging therapeutic approaches, such as antibody-toxin conjugates or CAR T cell therapies, offer potential by specifically targeting proteins on the glioblastoma cell surface. Combination strategies incorporating protein-targeted therapy and immune-based therapies demonstrate great promise for future clinical research. Moreover, gaining insights into the role of cell-of-origin in glioblastoma treatment response holds the potential to advance precision medicine approaches. Addressing these challenges is crucial to improving outcomes for glioblastoma patients and moving towards more effective precision therapies.
Control of TGFβ signalling by ubiquitination independent function of E3 ubiquitin ligase TRIP12
Authors: Keyan Kripa S , Salim Safa , Gowda Swetha , Abdelrahman Doua , Amir Syeda Sakina , Islam Zeyaul , Vargas Claire , Bengoechea-Alonso Maria Teresa , Alwa Amira , Dahal Subrat , Kolatkar Prasanna R. , Da’as Sahar , Torrisani Jerome , Ericsson Johan , Mohammad Farhan , Khan Omar M 
Published: October 2023

AbstractTransforming growth factor β (TGFβ) pathway is a master regulator of cell proliferation, differentiation, and death. Deregulation of TGFβ signalling is well established in several human diseases including autoimmune disorders and cancer. Thus, understanding molecular pathways governing TGFβ signalling may help better understand the underlying causes of some of those conditions. Here, we show that a HECT domain E3 ubiquitin ligase TRIP12 controls TGFβ signalling in multiple models. Interestingly, TRIP12 control of TGFβ signalling is completely independent of its E3 ubiquitin ligase activity. Instead, TRIP12 recruits SMURF2 to SMAD4, which is most likely responsible for inhibitory monoubiquitination of SMAD4, since SMAD4 monoubiquitination and its interaction with SMURF2 were dramatically downregulated in TRIP12-/- cells. Additionally, genetic inhibition of TRIP12 in human and murine cells leads to robust activation of TGFβ signalling which was rescued by re-introducing wildtype TRIP12 or a catalytically inactive C1959A mutant. Importantly, TRIP12 control of TGFβ signalling is evolutionary conserved. Indeed, genetic inhibition of Drosophila TRIP12 orthologue, ctrip, in gut leads to a reduced number of intestinal stem cells which was compensated by the increase in differentiated enteroendocrine cells. These effects were completely normalised in Drosophila strain where ctrip was co-inhibited together with Drosophila SMAD4 orthologue, Medea. Similarly, in murine 3D intestinal organoids, CRISPR/Cas9 mediated genetic targeting of Trip12 enhances TGFβ mediated proliferation arrest and cell death. Finally, CRISPR/Cas9 mediated genetic targeting of TRIP12 in MDA-MB-231 breast cancer cells enhances the TGFβ induced migratory capacity of these cells which was rescued to the wildtype level by re-introducing wildtype TRIP12. Our work establishes TRIP12 as an evolutionary conserved modulator of TGFβ signalling in health and disease.
RhoA balances microglial reactivity and survival during neuroinflammation
Authors: Socodato Renato , Rodrigues-Santos Artur , Tedim-Moreira Joana , Almeida Tiago O. , Canedo Teresa , Portugal Camila C. , Relvas João B. 
Published: October 2023

AbstractMicroglia are the largest myeloid cell population in the brain. During injury, disease, or inflammation, microglia adopt different functional states primarily involved in restoring brain homeostasis. However, sustained or exacerbated microglia inflammatory reactivity can lead to brain damage. Dynamic cytoskeleton reorganization correlates with alterations of microglial reactivity driven by external cues, and proteins controlling cytoskeletal reorganization, such as the Rho GTPase RhoA, are well positioned to refine or adjust the functional state of the microglia during injury, disease, or inflammation. Here, we use multi-biosensor-based live-cell imaging approaches and tissue-specific conditional gene ablation in mice to understand the role of RhoA in microglial response to inflammation. We found that a decrease in RhoA activity is an absolute requirement for microglial metabolic reprogramming and reactivity to inflammation. However, without RhoA, inflammation disrupts Ca2+ and pH homeostasis, dampening mitochondrial function, worsening microglial necrosis, and triggering microglial apoptosis. Our results suggest that a minimum level of RhoA activity is obligatory to concatenate microglia inflammatory reactivity and survival during neuroinflammation.
Perspective: Residual penile curvature correction during penile prosthesis implantation by plication in Peyronie’s patients
Authors: Chung Eric , Blecher Gideon 
Published: October 2023

AbstractFor patients with large calcified tunical plaque or severe corporal fibrosis which are likely to have a pronounced and persistent residual curvature which may not be correct by penile prosthesis implantation alone, other adjunctive manoeuvres such as penile plication and/or plaque incision with grafting may be necessary. The sequence between penile plication and penile prosthesis implantation is largely dependent on several factors such as the severity of penile curvature, the presence of (calcified) tunical plaque(s) and whether aggressive corporal dilation and subsequent penile remodelling with an inflated implant can straighten any residual penis curvature. The advantages of pre-placement of penile plication sutures prior to penile prosthesis implantation are the avoidance of inadvertent damage to the underlying penile prosthesis implant, the ability to adjust the tension on the rows of the plication sutures based on residual curvature with the device fully inflated, and potentially minimising the duration of surgery. In contrast, penile prosthesis implantation followed by penile plication to correct residual curvature, this sequence of surgery may negate the need for penile plications if penile remodelling is effective, or the residual curvature is less than 15 degrees where postoperative manual remodelling may continue to improve the penile cosmesis. When performed by expert surgeons and adhering to safe surgical principles, there is no doubt that patients will be satisfied with the outcomes and highly appreciative of the final penile cosmesis and the ensuing optimal outcomes.
An exact chiral amorphous spin liquid
Authors: Cassella G. , d’Ornellas P. , Hodson T. , Natori W. M. H. , Knolle J. 
Published: October 2023

AbstractTopological insulator phases of non-interacting particles have been generalized from periodic crystals to amorphous lattices, which raises the question whether topologically ordered quantum many-body phases may similarly exist in amorphous systems? Here we construct a soluble chiral amorphous quantum spin liquid by extending the Kitaev honeycomb model to random lattices with fixed coordination number three. The model retains its exact solubility but the presence of plaquettes with an odd number of sides leads to a spontaneous breaking of time reversal symmetry. We unearth a rich phase diagram displaying Abelian as well as a non-Abelian quantum spin liquid phases with a remarkably simple ground state flux pattern. Furthermore, we show that the system undergoes a finite-temperature phase transition to a conducting thermal metal state and discuss possible experimental realisations.
Disease-specific loss of microbial cross-feeding interactions in the human gut
Authors: Marcelino Vanessa R. , Welsh Caitlin , Diener Christian , Gulliver Emily L. , Rutten Emily L. , Young Remy B. , Giles Edward M. , Gibbons Sean M. , Greening Chris , Forster Samuel C. 
Published: October 2023

AbstractMany gut microorganisms critical to human health rely on nutrients produced by each other for survival; however, these cross-feeding interactions are still challenging to quantify and remain poorly characterized. Here, we introduce a Metabolite Exchange Score (MES) to quantify those interactions. Using metabolic models of prokaryotic metagenome-assembled genomes from over 1600 individuals, MES allows us to identify and rank metabolic interactions that are significantly affected by a loss of cross-feeding partners in 10 out of 11 diseases. When applied to a Crohn’s disease case-control study, our approach identifies a lack of species with the ability to consume hydrogen sulfide as the main distinguishing microbiome feature of disease. We propose that our conceptual framework will help prioritize in-depth analyses, experiments and clinical targets, and that targeting the restoration of microbial cross-feeding interactions is a promising mechanism-informed strategy to reconstruct a healthy gut ecosystem.
American crows that excel at tool use activate neural circuits distinct from less talented individuals
Authors: Pendergraft LomaJohn T. , Marzluff John M. , Cross Donna J. , Shimizu Toru , Templeton Christopher N. 
Published: October 2023

AbstractTools enable animals to exploit and command new resources. However, the neural circuits underpinning tool use and how neural activity varies with an animal’s tool proficiency, are only known for humans and some other primates. We use 18F-fluorodeoxyglucose positron emission tomography to image the brain activity of naïve vs trained American crows (Corvus brachyrhynchos) when presented with a task requiring the use of stone tools. As in humans, talent affects the neural circuits activated by crows as they prepare to execute the task. Naïve and less proficient crows use neural circuits associated with sensory- and higher-order processing centers (the mesopallium and nidopallium), while highly proficient individuals increase activity in circuits associated with motor learning and tactile control (hippocampus, tegmentum, nucleus basorostralis, and cerebellum). Greater proficiency is found primarily in adult female crows and may reflect their need to use more cognitively complex strategies, like tool use, to obtain food.
Dynamic neural representations of memory and space during human ambulatory navigation
Authors: Maoz Sabrina L. L. , Stangl Matthias , Topalovic Uros , Batista Daniel , Hiller Sonja , Aghajan Zahra M. , Knowlton Barbara , Stern John , Langevin Jean-Philippe , Fried Itzhak , Eliashiv Dawn , Suthana Nanthia 
Published: October 2023

AbstractOur ability to recall memories of personal experiences is an essential part of daily life. These episodic memories often involve movement through space and thus require continuous encoding of one’s position relative to the surrounding environment. The medial temporal lobe (MTL) is thought to be critically involved, based on studies in freely moving rodents and stationary humans. However, it remains unclear if and how the MTL represents both space and memory especially during physical navigation, given challenges associated with deep brain recordings in humans during movement. We recorded intracranial electroencephalographic (iEEG) activity while participants completed an ambulatory spatial memory task within an immersive virtual reality environment. MTL theta activity was modulated by successful memory retrieval or spatial positions within the environment, depending on dynamically changing behavioral goals. Altogether, these results demonstrate how human MTL oscillations can represent both memory and space in a temporally flexible manner during freely moving navigation.
Structural insights into the agonists binding and receptor selectivity of human histamine H4 receptor
Authors: Im Dohyun , Kishikawa Jun-ichi , Shiimura Yuki , Hisano Hiromi , Ito Akane , Fujita-Fujiharu Yoko , Sugita Yukihiko , Noda Takeshi , Kato Takayuki , Asada Hidetsugu , Iwata So 
Published: October 2023

AbstractHistamine is a biogenic amine that participates in allergic and inflammatory processes by stimulating histamine receptors. The histamine H4 receptor (H4R) is a potential therapeutic target for chronic inflammatory diseases such as asthma and atopic dermatitis. Here, we show the cryo-electron microscopy structures of the H4R-Gq complex bound with an endogenous agonist histamine or the selective agonist imetit bound in the orthosteric binding pocket. The structures demonstrate binding mode of histamine agonists and that the subtype-selective agonist binding causes conformational changes in Phe3447.39, which, in turn, form the “aromatic slot”. The results provide insights into the molecular underpinnings of the agonism of H4R and subtype selectivity of histamine receptors, and show that the H4R structures may be valuable in rational drug design of drugs targeting the H4R.
Resonant cavity phosphor
Authors: Lee Tae-Yun , Park Yeonsang , Jeon Heonsu 
Published: October 2023

AbstractWhile phosphors play an immensely important role in solid-state lighting and full-colour displays, it has been noted lately that their performance can be largely improved via structural engineering. Here, phosphor material is synergistically merged with yet another structurally engineered platform, resonant cavity (RC). When a 40-nm-thick colloidal quantum dot (CQD) film is embedded in a tailored RC with a moderate cavity quality factor (Q ≈ 90), it gains the ability to absorb the majority (~87%) of excitation photons, resulting in significantly enhanced CQD fluorescence (~29×) across a reasonably broad linewidth (~13 nm). The colour gamut covered by red and green pixels implemented using the RC phosphor—along with a broad bandwidth (~20 nm) blue excitation source—exceeds that of the sRGB standard (~121%). The simple planar geometry facilitates design and implementation of the RC phosphor, making it promising for use in real applications.
The airway microbiota of neonates colonized with asthma-associated pathogenic bacteria
Authors: Thorsen Jonathan , Li Xuan Ji , Peng Shuang , Sunde Rikke Bjersand , Shah Shiraz A. , Bhattacharyya Madhumita , Poulsen Casper Sahl , Poulsen Christina Egeø , Leal Rodriguez Cristina , Widdowson Michael , Neumann Avidan Uriel , Trivedi Urvish , Chawes Bo , Bønnelykke Klaus , Bisgaard Hans , Sørensen Søren J. , Stokholm Jakob 
Published: October 2023

AbstractCulture techniques have associated colonization with pathogenic bacteria in the airways of neonates with later risk of childhood asthma, whereas more recent studies utilizing sequencing techniques have shown the same phenomenon with specific anaerobic taxa. Here, we analyze nasopharyngeal swabs from 1 month neonates in the COPSAC2000prospective birth cohort by 16S rRNA gene sequencing of the V3-V4 region in relation to asthma risk throughout childhood. Results are compared with previous culture results from hypopharyngeal aspirates from the same cohort and with hypopharyngeal sequencing data from the later COPSAC2010cohort. Nasopharyngeal relative abundance values ofStreptococcus pneumoniae, Haemophilus influenzae, andMoraxella catarrhalisare associated with the same species in the hypopharyngeal cultures. A combined pathogen score of these bacteria’s abundance values is associated with persistent wheeze/asthma by age 7. No other taxa are associated. Compared to the hypopharyngeal aspirates from the COPSAC2010cohort, the anaerobesVeillonellaandPrevotella, which have previously been implicated in asthma development, are less commonly detected in the COPSAC2000nasopharyngeal samples, but correlate with the pathogen score, hinting at latent community structures that bridge current and previous results. These findings have implications for future asthma prevention efforts.
Preservation versus resection of Denonvilliers’ fascia in total mesorectal excision for male rectal cancer: follow-up analysis of the randomized PUF-01 trial
Authors: Fang Jiafeng , Wei Bo , Zheng Zongheng , Xiao Jian’an , Han Fanghai , Huang Meijin , Xu Qingwen , Wang Xiaozhong , Hong Chuyuan , Wang Gongping , Ju Yongle , Su Guoqiang , Deng Haijun , Zhang Jinxin , Li Jun , Yang Xiaofeng , Chen Tufeng , Huang Yong , Huang Jianglong , Liu Jianpei , Wei Hongbo ,   Chinese Postoperative Urogenital Function (PUF) Research Collaboration Group
Published: October 2023

AbstractTraditional total mesorectal excision (TME) for rectal cancer requires partial resection of Denonvilliers’ fascia (DVF), which leads to injury of pelvic autonomic nerve and postoperative urogenital dysfunction. It is still unclear whether entire preservation of DVF has better urogenital function and comparable oncological outcomes. We conducted a randomized clinical trial to investigate the superiority of DVF preservation over resection (NCT02435758). A total of 262 eligible male patients were randomized to Laparoscopic TME with DVF preservation (L-DVF-P group) or resection procedures (L-DVF-R group), 242 of which completed the study, including 122 cases of L-DVF-P and 120 cases of L-DVF-R. The initial analysis of the primary outcomes of urogenital function has previously been reported. Here, the updated analysis and secondary outcomes including 3-year survival (OS), 3-year disease-free survival (DFS), and recurrence rate between the two groups are reported for the modified intention-to-treat analysis, revealing no significant difference. In conclusion, L-DVF-P reveals better postoperative urogenital function and comparable oncological outcomes for male rectal cancer patients.
Imaging and multi-omics datasets converge to define different neural progenitor origins for ATRT-SHH subgroups
Authors: Lobón-Iglesias María-Jesús , Andrianteranagna Mamy , Han Zhi-Yan , Chauvin Céline , Masliah-Planchon Julien , Manriquez Valeria , Tauziede-Espariat Arnault , Turczynski Sandrina , Bouarich-Bourimi Rachida , Frah Magali , Dufour Christelle , Blauwblomme Thomas , Cardoen Liesbeth , Pierron Gaelle , Maillot Laetitia , Guillemot Delphine , Reynaud Stéphanie , Bourneix Christine , Pouponnot Célio , Surdez Didier , Bohec Mylene , Baulande Sylvain , Delattre Olivier , Piaggio Eliane , Ayrault Olivier , Waterfall Joshua J. , Servant Nicolas , Beccaria Kevin , Dangouloff-Ros Volodia , Bourdeaut Franck 
Published: October 2023

AbstractAtypical teratoid rhabdoid tumors (ATRT) are divided into MYC, TYR and SHH subgroups, suggesting diverse lineages of origin. Here, we investigate the imaging of human ATRT at diagnosis and the precise anatomic origin of brain tumors in the Rosa26-CreERT2::Smarcb1flox/flox model. This cross-species analysis points to an extra-cerebral origin for MYC tumors. Additionally, we clearly distinguish SHH ATRT emerging from the cerebellar anterior lobe (CAL) from those emerging from the basal ganglia (BG) and intra-ventricular (IV) regions. Molecular characteristics point to the midbrain-hindbrain boundary as the origin of CAL SHH ATRT, and to the ganglionic eminence as the origin of BG/IV SHH ATRT. Single-cell RNA sequencing on SHH ATRT supports these hypotheses. Trajectory analyses suggest that SMARCB1 loss induces a de-differentiation process mediated by repressors of the neuronal program such as REST, ID and the NOTCH pathway.
Single virus fingerprinting by widefield interferometric defocus-enhanced mid-infrared photothermal microscopy
Authors: Xia Qing , Guo Zhongyue , Zong Haonan , Seitz Scott , Yurdakul Celalettin , Ünlü M. Selim , Wang Le , Connor John H. , Cheng Ji-Xin 
Published: October 2023

AbstractClinical identification and fundamental study of viruses rely on the detection of viral proteins or viral nucleic acids. Yet, amplification-based and antigen-based methods are not able to provide precise compositional information of individual virions due to small particle size and low-abundance chemical contents (e.g., ~ 5000 proteins in a vesicular stomatitis virus). Here, we report a widefield interferometric defocus-enhanced mid-infrared photothermal (WIDE-MIP) microscope for high-throughput fingerprinting of single viruses. With the identification of feature absorption peaks, WIDE-MIP reveals the contents of viral proteins and nucleic acids in single DNA vaccinia viruses and RNA vesicular stomatitis viruses. Different nucleic acid signatures of thymine and uracil residue vibrations are obtained to differentiate DNA and RNA viruses. WIDE-MIP imaging further reveals an enriched β sheet components in DNA varicella-zoster virus proteins. Together, these advances open a new avenue for compositional analysis of viral vectors and elucidating protein function in an assembled virion.