bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combinatorial treatment with statins and niclosamide prevents CRC dissemination by unhinging the MACC1-β-catenin-S100A4 axis of metastasis
Authors: Kortüm Benedikt , Radhakrishnan Harikrishnan , Zincke Fabian , Sachse Christoph , Burock Susen , Keilholz Ulrich , Dahlmann Mathias , Walther Wolfgang , Dittmar Gunnar , Kobelt Dennis , Stein Ulrike 
Published: August 2022

AbstractColorectal cancer (CRC) is the second-most common malignant disease worldwide, and metastasis is the main culprit of CRC-related death. Metachronous metastases remain to be an unpredictable, unpreventable, and fatal complication, and tracing the molecular chain of events that lead to metastasis would provide mechanistically linked biomarkers for the maintenance of remission in CRC patients after curative treatment. We hypothesized, that Metastasis-associated in colorectal cancer-1 (MACC1) induces a secretory phenotype to enforce metastasis in a paracrine manner, and found, that the cell-free culture medium of MACC1-expressing CRC cells induces migration. Stable isotope labeling by amino acids in cell culture mass spectrometry (SILAC-MS) of the medium revealed, that S100A4 is significantly enriched in the MACC1-specific secretome. Remarkably, both biomarkers correlate in expression data of independent cohorts as well as within CRC tumor sections. Furthermore, combined elevated transcript levels of the metastasis genes MACC1 and S100A4 in primary tumors and in blood plasma robustly identifies CRC patients at high risk for poor metastasis-free (MFS) and overall survival (OS). Mechanistically, MACC1 strengthens the interaction of β-catenin with TCF4, thus inducing S100A4 synthesis transcriptionally, resulting in elevated secretion to enforce cell motility and metastasis. In cell motility assays, S100A4 was indispensable for MACC1-induced migration, as shown via knock-out and pharmacological inhibition of S100A4. The direct transcriptional and functional relationship of MACC1 and S100A4 was probed by combined targeting with repositioned drugs. In fact, the MACC1-β-catenin-S100A4 axis by statins (MACC1) and niclosamide (S100A4) synergized in inhibiting cancer cell motility in vitro and metastasis in vivo. The MACC1-β-catenin-S100A4 signaling axis is causal for CRC metastasis. Selectively repositioned drugs synergize in restricting MACC1/S100A4-driven metastasis with cross-entity potential.
A high-throughput drug screen reveals means to differentiate triple-negative breast cancer
Authors: Vulin Milica , Jehanno Charly , Sethi Atul , Correia Ana Luísa , Obradović Milan M. S. , Couto Joana Pinto , Coissieux Marie-May , Diepenbruck Maren , Preca Bogdan-Tiberius , Volkmann Katrin , der Maur Priska Auf , Schmidt Alexander , Münst Simone , Sauteur Loïc , Kloc Michal , Palafox Marta , Britschgi Adrian , Unterreiner Vincent , Galuba Olaf , Claerr Isabelle , Lopez-Romero Sandra , Galli Giorgio G. , Baeschlin Daniel , Okamoto Ryoko , Soysal Savas D. , Mechera Robert , Weber Walter P. , Radimerski Thomas , Bentires-Alj Mohamed 
Published: August 2022

AbstractPlasticity delineates cancer subtypes with more or less favourable outcomes. In breast cancer, the subtype triple-negative lacks expression of major differentiation markers, e.g., estrogen receptor α (ERα), and its high cellular plasticity results in greater aggressiveness and poorer prognosis than other subtypes. Whether plasticity itself represents a potential vulnerability of cancer cells is not clear. However, we show here that cancer cell plasticity can be exploited to differentiate triple-negative breast cancer (TNBC). Using a high-throughput imaging-based reporter drug screen with 9 501 compounds, we have identified three polo-like kinase 1 (PLK1) inhibitors as major inducers of ERα protein expression and downstream activity in TNBC cells. PLK1 inhibition upregulates a cell differentiation program characterized by increased DNA damage, mitotic arrest, and ultimately cell death. Furthermore, cells surviving PLK1 inhibition have decreased tumorigenic potential, and targeting PLK1 in already established tumours reduces tumour growth both in cell line- and patient-derived xenograft models. In addition, the upregulation of genes upon PLK1 inhibition correlates with their expression in normal breast tissue and with better overall survival in breast cancer patients. Our results indicate that differentiation therapy based on PLK1 inhibition is a potential alternative strategy to treat TNBC.
Patient trajectories after diagnosis of diffuse large B-cell lymphoma—a multistate modelling approach to estimate the chance of lasting remission
Authors: Ekberg Sara , Crowther Michael , Harrysson Sara , Jerkeman Mats , E. Smedby Karin , Eloranta Sandra 
Published: August 2022

Abstract
Background
Achieving lasting remission for at least 2 years is a good indicator for favourable prognosis long term after Diffuse large B-cell lymphoma (DLBCL). The aim of this study was to provide real-world probabilities, useful in risk communication and clinical decision-making, of the chance for lasting remissions by clinical characteristics.

Methods
DLBCL patients in remission after primary treatment recorded in the Swedish Lymphoma register 2007–2014 (n = 2941) were followed for relapse and death using multistate models to study patient trajectories. Flexible parametric models were used to estimate transition rates.

Results
At 2 years, 80.7% (95% CI: 79.0–82.2) of the patients were predicted to remain in remission and 13.2% (95% CI: 11.9–14.6) to have relapsed. The relapse risk peaked at 7 months, and the annual decline of patients in remission stabilised after 2 years. The majority of patients in the second remission transitioned into a new relapse. The probability of a lasting remission was reduced by 20.4% units for patients with IPI 4–5 compared to patients with IPI 0–1, and time in remission was shortened by 3.5 months.

Conclusion
The long-term prognosis was overall favourable with 80% achieving durable first remissions. However, prognosis varied by clinical subgroups and relapsing patients seldom achieved durable second remissions.
Circular RNA hsa_circ_0007367 promotes the progression of pancreatic ductal adenocarcinoma by sponging miR-6820-3p and upregulating YAP1 expression
Authors: Zhang Haocheng , Ma Xiaolei , Wang Luning , Li Xinyu , Feng Di , Liu Meiming , Li Jiayang , Cheng Mengxing , Song Na , Yang Xinxia , Ba Lina , Lei Yating , Zhang Ruipu , Zhu Yunxiao , Xu Wenxiao , Qiao Guofen 
Published: August 2022

AbstractCircular RNAs (circRNAs) play critical regulatory roles in cancer biological processes. Nevertheless, the contributions and underlying mechanisms of circRNAs to pancreatic ductal adenocarcinoma (PDAC) remain largely unexplored. Dysregulated circRNAs between cancerous tissues and matched adjacent normal tissues were identified by circRNA microarray in PDAC. The biological effect of hsa_circ_007367 both in vitro and in vivo was demonstrated by gain- and loss-of-function experiments. Further, dual-luciferase reporter and RNA pull-down assays were performed to confirm the interaction among hsa_circ_007367, miR-6820-3p, and Yes-associated protein 1 (YAP1). The expression of hsa_circ_007367 and YAP1 were detected by in situ hybridization (ISH) and immunohistochemistry (IHC) using tissue microarray (TMA) in 128 PDAC samples. We first identified that a novel circRNA, hsa_circ_0007367, was markedly upregulated in PDAC tissues and cells. Functionally, in vivo and in vitro data indicated that hsa_circ_0007367 promotes the proliferation and metastasis of PDAC. Mechanistically, we confirmed that hsa_circ_0007367 could facilitate the expression of YAP1, a well-known oncogene, by sponging miR-6820-3p, which function as a tumor suppresser in PDAC cells. The results of ISH and IHC demonstrated that hsa_circ_0007367 and YAP1 were upregulated in PDAC tissues. Furthermore, clinical data showed that higher hsa_circ_0007367 expression was correlated with advanced histological grade and lymph node metastasis in PDAC patients. In conclusion, our findings reveal that hsa_circ_0007367 acts as an oncogene via modulating miR-6820-3p/YAP1 axis to promote the progression of PDAC, and suggest that hsa_circ_0007367 may serve as a potential therapeutic target for treatment of PDAC.
The microRNA-10b-Bim axis promotes cancer progression through activating autophagy in oral squamous cell carcinoma
Authors: Li Shaoming , Gao Ling , Liu Jiacheng , Guo Chao , Zheng Jingjing , Zhi Keqian , Ren Wenhao 
Published: August 2022

AbstractAutophagy is related to many cellular mechanisms and dysregulation of autophagy involves the pathological process in cancer. miR-10b activates autophagy, which promotes invasion and migration of OSCC. Its functional role in the mechanism of OSCC to autophagy remains to be unclear. Overexpression of miR-10b was followed by enhanced OSCC invasion and migration and activated autophagic protein, such as LC3II/ATG5. MiR-10b attracted Bim directly according to the Bio-informatics analyses and double luciferases reporter assays. Functional experiments further revealed that miR-10b could promote invasion and migration in vitro. In addition, miR-10b induced autophagy via inhibiting Bim in invasion and migration of OSCC. Notably, animal experiments confirmed that miR-10b-Bim promoted proliferation and autophagy in OSCC. In addition, this study provides a theoretical support for regulating the mechanism of OSCC by inducing autophagy with miR-10b-Bim as a target.
Cholinergic basal forebrain nucleus of Meynert regulates chronic pain-like behavior via modulation of the prelimbic cortex
Authors: Oswald Manfred J. , Han Yechao , Li Han , Marashli Samuel , Oglo Deniz Nouri , Ojha Bhavya , Naser Paul V. , Gan Zheng , Kuner Rohini 
Published: August 2022

AbstractThe basal nucleus of Meynert (NBM) subserves critically important functions in attention, arousal and cognition via its profound modulation of neocortical activity and is emerging as a key target in Alzheimer’s and Parkinson’s dementias. Despite the crucial role of neocortical domains in pain perception, however, the NBM has not been studied in models of chronic pain. Here, using in vivo tetrode recordings in behaving mice, we report that beta and gamma oscillatory activity is evoked in the NBM by noxious stimuli and is facilitated at peak inflammatory pain-like behavior. Optogenetic and chemogenetic cell-specific, reversible manipulations of NBM cholinergic-GABAergic neurons reveal their role in endogenous control of nociceptive hypersensitivity, which are manifest via projections to the prelimbic cortex, resulting in layer 5-mediated antinociception. Our data unravel the importance of the NBM in top-down control of neocortical processing of pain-like behavior.
An interplay between cellular growth and atypical fusion defines morphogenesis of a modular glial niche in Drosophila
Authors: Rujano Maria Alexandra , Briand David , Ðelić Bojana , Marc Julie , Spéder Pauline 
Published: August 2022

AbstractNeural stem cells (NSCs) live in an intricate cellular microenvironment supporting their activity, the niche. Whilst shape and function are inseparable, the morphogenetic aspects of niche development are poorly understood. Here, we use the formation of a glial niche to investigate acquisition of architectural complexity. Cortex glia (CG) in Drosophila regulate neurogenesis and build a reticular structure around NSCs. We first show that individual CG cells grow tremendously to ensheath several NSC lineages, employing elaborate proliferative mechanisms which convert these cells into syncytia rich in cytoplasmic bridges. CG syncytia further undergo homotypic cell–cell fusion, using defined cell surface receptors and actin regulators. Cellular exchange is however dynamic in space and time. This atypical cell fusion remodels cellular borders, restructuring the CG syncytia. Ultimately, combined growth and fusion builds the multi-level architecture of the niche, and creates a modular, spatial partition of the NSC population. Our findings provide insights into how a niche forms and organises while developing intimate contacts with a stem cell population.
Designed peptides as nanomolar cross-amyloid inhibitors acting via supramolecular nanofiber co-assembly
Authors: Taş Karin , Volta Beatrice Dalla , Lindner Christina , El Bounkari Omar , Hille Kathleen , Tian Yuan , Puig-Bosch Xènia , Ballmann Markus , Hornung Simon , Ortner Martin , Prem Sophia , Meier Laura , Rammes Gerhard , Haslbeck Martin , Weber Christian , Megens Remco T. A. , Bernhagen Jürgen , Kapurniotu Aphrodite 
Published: August 2022

AbstractAmyloid self-assembly is linked to numerous devastating cell-degenerative diseases. However, designing inhibitors of this pathogenic process remains a major challenge. Cross-interactions between amyloid-β peptide (Aβ) and islet amyloid polypeptide (IAPP), key polypeptides of Alzheimer’s disease (AD) and type 2 diabetes (T2D), have been suggested to link AD with T2D pathogenesis. Here, we show that constrained peptides designed to mimic the Aβ amyloid core (ACMs) are nanomolar cross-amyloid inhibitors of both IAPP and Aβ42 and effectively suppress reciprocal cross-seeding. Remarkably, ACMs act by co-assembling with IAPP or Aβ42 into amyloid fibril-resembling but non-toxic nanofibers and their highly ordered superstructures. Co-assembled nanofibers exhibit various potentially beneficial features including thermolability, proteolytic degradability, and effective cellular clearance which are reminiscent of labile/reversible functional amyloids. ACMs are thus promising leads for potent anti-amyloid drugs in both T2D and AD while the supramolecular nanofiber co-assemblies should inform the design of novel functional (hetero-)amyloid-based nanomaterials for biomedical/biotechnological applications.
Radial bound states in the continuum for polarization-invariant nanophotonics
Authors: Kühner Lucca , Sortino Luca , Berté Rodrigo , Wang Juan , Ren Haoran , Maier Stefan A. , Kivshar Yuri , Tittl Andreas 
Published: August 2022

AbstractAll-dielectric nanophotonics underpinned by the physics of bound states in the continuum (BICs) have demonstrated breakthrough applications in nanoscale light manipulation, frequency conversion and optical sensing. Leading BIC implementations range from isolated nanoantennas with localized electromagnetic fields to symmetry-protected metasurfaces with controllable resonance quality (Q) factors. However, they either require structured light illumination with complex beam-shaping optics or large, fabrication-intense arrays of polarization-sensitive unit cells, hindering tailored nanophotonic applications and on-chip integration. Here, we introduce radial quasi-bound states in the continuum (radial BICs) as a new class of radially distributed electromagnetic modes controlled by structural asymmetry in a ring of dielectric rod pair resonators. The radial BIC platform provides polarization-invariant and tunable high-Q resonances with strongly enhanced near fields in an ultracompact footprint as low as 2 µm2. We demonstrate radial BIC realizations in the visible for sensitive biomolecular detection and enhanced second-harmonic generation from monolayers of transition metal dichalcogenides, opening new perspectives for compact, spectrally selective, and polarization-invariant metadevices for multi-functional light-matter coupling, multiplexed sensing, and high-density on-chip photonics.
Strong and Localized Luminescence from Interface Bubbles Between Stacked hBN Multilayers
Authors: Lee Hae Yeon , Sarkar Soumya , Reidy Kate , Kumar Abinash , Klein Julian , Watanabe Kenji , Taniguchi Takashi , LeBeau James M. , Ross Frances M. , Gradečak Silvija 
Published: August 2022

AbstractExtraordinary optoelectronic properties of van der Waals (vdW) heterostructures can be tuned via strain caused by mechanical deformation. Here, we demonstrate strong and localized luminescence in the ultraviolet region from interface bubbles between stacked multilayers of hexagonal boron nitride (hBN). Compared to bubbles in stacked monolayers, bubbles formed by stacking vdW multilayers show distinct mechanical behavior. We use this behavior to elucidate radius- and thickness-dependent bubble geometry and the resulting strain across the bubble, from which we establish the thickness-dependent bending rigidity of hBN multilayers. We then utilize the polymeric material confined within the bubbles to modify the bubble geometry under electron beam irradiation, resulting in strong luminescence and formation of optical standing waves. Our results open a route to design and modulate microscopic-scale optical cavities via strain engineering in vdW materials, which we suggest will be relevant to both fundamental mechanical studies and optoelectronic applications.
Discrete subicular circuits control generalization of hippocampal seizures
Authors: Fei Fan , Wang Xia , Xu Cenglin , Shi Jiaying , Gong Yiwei , Cheng Heming , Lai Nanxi , Ruan Yeping , Ding Yao , Wang Shuang , Chen Zhong , Wang Yi 
Published: August 2022

AbstractEpilepsy is considered a circuit-level dysfunction associated with imbalanced excitation-inhibition, it is therapeutically necessary to identify key brain regions and related circuits in epilepsy. The subiculum is an essential participant in epileptic seizures, but the circuit mechanism underlying its role remains largely elusive. Here we deconstruct the diversity of subicular circuits in a mouse model of epilepsy. We find that excitatory subicular pyramidal neurons heterogeneously control the generalization of hippocampal seizures by projecting to different downstream regions. Notably, anterior thalamus-projecting subicular neurons bidirectionally mediate seizures, while entorhinal cortex-projecting subicular neurons act oppositely in seizure modulation. These two subpopulations are structurally and functionally dissociable. An intrinsically enhanced hyperpolarization-activated current and robust bursting intensity in anterior thalamus-projecting neurons facilitate synaptic transmission, thus contributing to the generalization of hippocampal seizures. These results demonstrate that subicular circuits have diverse roles in epilepsy, suggesting the necessity to precisely target specific subicular circuits for effective treatment of epilepsy.
Selective suppression of melanoma lacking IFN-γ pathway by JAK inhibition depends on T cells and host TNF signaling
Authors: Shen Hongxing , Huang Fengyuan , Zhang Xiangmin , Ojo Oluwagbemiga A. , Li Yuebin , Trummell Hoa Quang , Anderson Joshua C. , Fiveash John , Bredel Markus , Yang Eddy S. , Willey Christopher D. , Chong Zechen , Bonner James A. , Shi Lewis Zhichang 
Published: August 2022

AbstractTherapeutic resistance to immune checkpoint blockers (ICBs) in melanoma patients is a pressing issue, of which tumor loss of IFN-γ signaling genes is a major underlying mechanism. However, strategies of overcoming this resistance mechanism have been largely elusive. Moreover, given the indispensable role of tumor-infiltrating T cells (TILs) in ICBs, little is known about how tumor-intrinsic loss of IFN-γ signaling (IFNγR1KO) impacts TILs. Here, we report that IFNγR1KOmelanomas have reduced infiltration and function of TILs. IFNγR1KOmelanomas harbor a network of constitutively active protein tyrosine kinases centered on activated JAK1/2. Mechanistically, JAK1/2 activation is mediated by augmented mTOR. Importantly, JAK1/2 inhibition with Ruxolitinib selectively suppresses the growth of IFNγR1KObut not scrambled control melanomas, depending on T cells and host TNF. Together, our results reveal an important role of tumor-intrinsic IFN-γ signaling in shaping TILs and manifest a targeted therapy to bypass ICB resistance of melanomas defective of IFN-γ signaling.
Mechanism of peptides from rice hydrolyzed proteins hindering starch digestion subjected to hydrothermal treatment
Authors: Lu Xiaoxue , Ma Rongrong , Zhan Jinling , Jin Zhengyu , Tian Yaoqi 
Published: August 2022

AbstractClarifying the interactions between food components is critical in designing carbohydrate-based foods with low digestibility. To date, the hindering effect of starch-protein interactions on starch digestion has attracted extensive attention. In this study, rice proteins were further hydrolyzed, and rice peptides (RP) with different molecular weights were obtained by ultrafiltration. The effects and possible mechanisms of RP with different molecular weights on the structure, thermal properties, and in vitro digestibility of cooked rice starch were investigated. All peptides slowed the digestion of rice starch in a concentration-dependent manner. A concentration of 10% RP>10 decreased the rapidly digestible starch content from 68.02 to 45.90 g/100 g, and increased the resistant starch content from 17.54 to 36.54 g/100 g. The addition of RP improved the thermal stability of the starch and reduced the amount of leached amylose. Infrared analysis shows that strong hydrogen bonds formed between RP (especially RP>10) and starch during co-gelatinization. In addition, RP improved the compactness of aggregated structure and played an important role in hindering the enzymatic hydrolysis of starch. These results enrich the theory of starch-protein interactions and have important implications for the development of carbohydrate-based foods with low digestibility and protein functional foods.
Directed information flow during laparoscopic surgical skill acquisition dissociated skill level and medical simulation technology
Authors: Kamat Anil , Makled Basiel , Norfleet Jack , Schwaitzberg Steven D. , Intes Xavier , De Suvranu , Dutta Anirban 
Published: August 2022

AbstractVirtual reality (VR) simulator has emerged as a laparoscopic surgical skill training tool that needs validation using brain–behavior analysis. Therefore, brain network and skilled behavior relationship were evaluated using functional near-infrared spectroscopy (fNIRS) from seven experienced right-handed surgeons and six right-handed medical students during the performance of Fundamentals of Laparoscopic Surgery (FLS) pattern of cutting tasks in a physical and a VR simulator. Multiple regression and path analysis (MRPA) found that the FLS performance score was statistically significantly related to the interregional directed functional connectivity from the right prefrontal cortex to the supplementary motor area with F (2, 114) = 9, p < 0.001, and R2 = 0.136. Additionally, a two-way multivariate analysis of variance (MANOVA) found a statistically significant effect of the simulator technology on the interregional directed functional connectivity from the right prefrontal cortex to the left primary motor cortex (F (1, 15) = 6.002, p = 0.027; partial η2 = 0.286) that can be related to differential right-lateralized executive control of attention. Then, MRPA found that the coefficient of variation (CoV) of the FLS performance score was statistically significantly associated with the CoV of the interregionally directed functional connectivity from the right primary motor cortex to the left primary motor cortex and the left primary motor cortex to the left prefrontal cortex with F (2, 22) = 3.912, p = 0.035, and R2 = 0.262. This highlighted the importance of the efference copy information from the motor cortices to the prefrontal cortex for postulated left-lateralized perceptual decision-making to reduce behavioral variability.