bluuebunny/crossref_metadata_2025_split huggingface dataset:
MAPK-pathway inhibition mediates inflammatory reprogramming and sensitizes tumors to targeted activation of innate immunity sensor RIG-I
Authors: Brägelmann Johannes , Lorenz Carina , Borchmann Sven , Nishii Kazuya , Wegner Julia , Meder Lydia , Ostendorp Jenny , Ast David F. , Heimsoeth Alena , Nakasuka Takamasa , Hirabae Atsuko , Okawa Sachi , Dammert Marcel A. , Plenker Dennis , Klein Sebastian , Lohneis Philipp , Gu Jianing , Godfrey Laura K. , Forster Jan , Trajkovic-Arsic Marija , Zillinger Thomas , Haarmann Mareike , Quaas Alexander , Lennartz Stefanie , Schmiel Marcel , D’Rozario Joshua , Thomas Emily S. , Li Henry , Schmitt Clemens A. , George Julie , Thomas Roman K. , von Karstedt Silvia , Hartmann Gunther , Büttner Reinhard , Ullrich Roland T. , Siveke Jens T. , Ohashi Kadoaki , Schlee Martin , Sos Martin L. 
Published: September 2021

AbstractKinase inhibitors suppress the growth of oncogene driven cancer but also enforce the selection of treatment resistant cells that are thought to promote tumor relapse in patients. Here, we report transcriptomic and functional genomics analyses of cells and tumors within their microenvironment across different genotypes that persist during kinase inhibitor treatment. We uncover a conserved, MAPK/IRF1-mediated inflammatory response in tumors that undergo stemness- and senescence-associated reprogramming. In these tumor cells, activation of the innate immunity sensor RIG-I via its agonist IVT4, triggers an interferon and a pro-apoptotic response that synergize with concomitant kinase inhibition. In humanized lung cancer xenografts and a syngeneic Egfr-driven lung cancer model these effects translate into reduction of exhausted CD8+ T cells and robust tumor shrinkage. Overall, the mechanistic understanding of MAPK/IRF1-mediated intratumoral reprogramming may ultimately prolong the efficacy of targeted drugs in genetically defined cancer patients.
A cell-free nanobody engineering platform rapidly generates SARS-CoV-2 neutralizing nanobodies
Authors: Chen Xun , Gentili Matteo , Hacohen Nir , Regev Aviv 
Published: September 2021

AbstractAntibody engineering technologies face increasing demands for speed, reliability and scale. We develop CeVICA, a cell-free nanobody engineering platform that uses ribosome display for in vitro selection of nanobodies from a library of 1011 randomized sequences. We apply CeVICA to engineer nanobodies against the Receptor Binding Domain (RBD) of SARS-CoV-2 spike protein and identify >800 binder families using a computational pipeline based on CDR-directed clustering. Among 38 experimentally-tested families, 30 are true RBD binders and 11 inhibit SARS-CoV-2 pseudotyped virus infection. Affinity maturation and multivalency engineering increase nanobody binding affinity and yield a virus neutralizer with picomolar IC50. Furthermore, the capability of CeVICA for comprehensive binder prediction allows us to validate the fitness of our nanobody library. CeVICA offers an integrated solution for rapid generation of divergent synthetic nanobodies with tunable affinities in vitro and may serve as the basis for automated and highly parallel nanobody engineering.
Mixing between chemically variable primitive basalts creates and modifies crystal cargoes
Authors: Neave David A. , Beckmann Philipp , Behrens Harald , Holtz François 
Published: September 2021

AbstractBasaltic crystal cargoes often preserve records of mantle-derived chemical variability that have been erased from their carrier liquids by magma mixing. However, the consequences of mixing between similarly primitive but otherwise chemically variable magmas remain poorly understood despite ubiquitous evidence of chemical variability in primary melt compositions and mixing-induced disequilibrium within erupted crystal cargoes. Here we report observations from magma–magma reaction experiments performed on analogues of primitive Icelandic lavas derived from distinct mantle sources to determine how their crystal cargoes respond to mixing-induced chemical disequilibrium. Chemical variability in our experimental products is controlled dominantly by major element diffusion in the melt that alters phase equilibria and triggers plagioclase resorption within regions that were initially plagioclase saturated. Isothermal mixing between chemically variable basaltic magmas may therefore play important but previously underappreciated roles in creating and modifying crystal cargoes by unlocking plagioclase-rich mushes and driving resorption, (re-)crystallisation and solid-state diffusion.
Synthetic essentiality between PTEN and core dependency factor PAX7 dictates rhabdomyosarcoma identity
Authors: Langdon Casey G. , Gadek Katherine E. , Garcia Matthew R. , Evans Myron K. , Reed Kristin B. , Bush Madeline , Hanna Jason A. , Drummond Catherine J. , Maguire Matthew C. , Leavey Patrick J. , Finkelstein David , Jin Hongjian , Schreiner Patrick A. , Rehg Jerold E. , Hatley Mark E. 
Published: September 2021

AbstractPTENpromoter hypermethylation is nearly universal andPTENcopy number loss occurs in ~25% of fusion-negative rhabdomyosarcoma (FN-RMS). Here we showPtendeletion in a mouse model of FN-RMS results in less differentiated tumors more closely resembling human embryonal RMS. PTEN loss activated the PI3K pathway but did not increase mTOR activity. In wild-type tumors, PTEN was expressed in the nucleus suggesting loss of nuclear PTEN functions could account for these phenotypes.Ptendeleted tumors had increased expression of transcription factors important in neural and skeletal muscle development includingDbx1andPax7.Pax7deletion completely rescued the effects ofPtenloss. Strikingly, thesePten;Pax7deleted tumors were no longer FN-RMS but displayed smooth muscle differentiation similar to leiomyosarcoma. These data highlight howPtenloss in FN-RMS is connected to a PAX7 lineage-specific transcriptional output that creates a dependency or synthetic essentiality on the transcription factor PAX7 to maintain tumor identity.
Trigger point injection for post-mastectomy pain: a simple intervention with high rate of long-term relief
Authors: Khoury Amal L. , Keane Holly , Varghese Flora , Hosseini Ava , Mukhtar Rita , Eder Suzanne E. , Weinstein Philip R. , Esserman Laura J. 
Published: September 2021

AbstractPost-mastectomy pain syndrome (PMPS) is a common and often debilitating condition. The syndrome is defined by chest wall pain unresponsive to standard pain medications and the presence of exquisite point tenderness along the inframammary fold at the site of the T4 and T5 cutaneous intercostal nerve branches as they exit from the chest wall. Pressure at the site triggers and reproduces the patient’s spontaneous or motion-evoked pain. The likely pathogenesis is neuroma formation after injury to the T4 and T5 intercostal nerves during breast surgery. We assessed the rate of long-term resolution of post-mastectomy pain after trigger point injections (2 mL of 1:1 mixture of 0.5% bupivacaine and 4 mg/mL dexamethasone) to relieve neuropathic pain in a prospective single-arm cohort study. Fifty-two women (aged 31–92) who underwent partial mastectomy with reduction mammoplasty or mastectomy with or without reconstruction, and who presented with PMPS were enrolled at the University of California San Francisco Breast Care Center from August 2010 through April 2018. The primary outcome was a long-term resolution of pain, defined as significant or complete relief of pain for greater than 3 months. A total of 91 trigger points were treated with mean follow-up 43.9 months with a 91.2% (83/91) success rate. Among those with a long-term resolution of pain, 60 trigger points (72.3%) required a single injection to achieve long-lasting relief. Perineural infiltration with bupivacaine and dexamethasone is a safe, simple, and effective treatment for PMPS presenting as trigger point pain along the inframammary fold.
Iminodibenzyl induced redirected COX-2 activity inhibits breast cancer progression
Authors: Shah Harshit , Pang Lizhi , Qian Steven , Sathish Venkatachalem 
Published: September 2021

AbstractKnocking down delta-5-desaturase (D5D) by siRNA or shRNA is a promising strategy to achieve 8-hydroxyoctanoic acid (8-HOA) production for cancer inhibition. However, the RNAi-based strategy to stimulate 8-HOA is restricted due to endonucleases mediated physiological degradation and off-target effects. Thus, to get persistent 8-HOA in the cancer cell, we recognized a D5D inhibitor Iminodibenzyl. Here, we have postulated that Iminodibenzyl, by inhibiting D5D activity, could shift the di-homo-gamma-linolenic acid (DGLA) peroxidation from arachidonic acid to 8-HOA in high COX-2 microenvironment of 4T1 and MDA-MB-231 breast cancer cells. We observed that Iminodibenzyl stimulated 8-HOA caused HDAC activity reduction resulting in intrinsic apoptosis pathway activation. Additionally, reduced filopodia and lamellipodia, and epithelial-mesenchymal transition markers give rise to decreased cancer cell migration. In the orthotopic breast cancer model, the combination of Iminodibenzyl and DGLA reduced tumor size. From in vitro and in vivo studies, we concluded that Iminodibenzyl could reprogram COX-2 induced DGLA peroxidation to produce anti-cancer activity.
Effects of microgravity exposure and fructo-oligosaccharide ingestion on the proteome of soleus and extensor digitorum longus muscles in developing mice
Authors: Ohira Takashi , Ino Yoko , Kimura Yayoi , Nakai Yusuke , Kimura Ayuko , Kurata Yoichi , Kagawa Hiroyuki , Kimura Mitsuo , Egashira Kenji , Matsuda Chie , Ohira Yoshinobu , Furukawa Satoshi , Hirano Hisashi 
Published: September 2021

AbstractShort-chain fatty acids produced by the gut bacterial fermentation of non-digestible carbohydrates, e.g., fructo-oligosaccharide (FOS), contribute to the maintenance of skeletal muscle mass and oxidative metabolic capacity. We evaluated the effect of FOS ingestion on protein expression of soleus (Sol) and extensor digitorum longus muscles in mice exposed to microgravity (μ-g). Twelve 9-week-old male C57BL/6J mice were raised individually on the International Space Station under μ-g or artificial 1-g and fed a diet with or without FOS (n = 3/group). Regardless of FOS ingestion, the absolute wet weights of both muscles tended to decrease, and the fiber phenotype in Sol muscles shifted toward fast-twitch type following μ-g exposure. However, FOS ingestion tended to mitigate the μ-g-exposure-related decrease in oxidative metabolism and enhance glutathione redox detoxification in Sol muscles. These results indicate that FOS ingestion mildly suppresses metabolic changes and oxidative stress in antigravity Sol muscles during spaceflight.
Technology-based therapy-response and prognostic biomarkers in a prospective study of a de novo Parkinson’s disease cohort
Authors: Di Lazzaro Giulia , Ricci Mariachiara , Saggio Giovanni , Costantini Giovanni , Schirinzi Tommaso , Alwardat Mohammad , Pietrosanti Luca , Patera Martina , Scalise Simona , Giannini Franco , Pisani Antonio 
Published: September 2021

AbstractEarly noninvasive reliable biomarkers are among the major unmet needs in Parkinson’s disease (PD) to monitor therapy response and disease progression. Objective measures of motor performances could allow phenotyping of subtle, undetectable, early stage motor impairments of PD patients. This work aims at identifying prognostic biomarkers in newly diagnosed PD patients and quantifying therapy-response. Forty de novo PD patients underwent clinical and technology-based kinematic assessments performing motor tasks (MDS-UPDRS part III) to assess tremor, bradykinesia, gait, and postural stability (T0). A visit after 6 months (T1) and a clinical and kinematic assessment after 12 months (T2) where scheduled. A clinical follow-up was provided between 30 and 36 months after the diagnosis (T3). We performed an ANOVA for repeated measures to compare patients’ kinematic features at baseline and at T2 to assess therapy response. Pearson correlation test was run between baseline kinematic features and UPDRS III score variation between T0 and T3, to select candidate kinematic prognostic biomarkers. A multiple linear regression model was created to predict the long-term motor outcome using T0 kinematic measures. All motor tasks significantly improved after the dopamine replacement therapy. A significant correlation was found between UPDRS scores variation and some baseline bradykinesia (toe tapping amplitude decrement, p = 0.009) and gait features (velocity of arms and legs, sit-to-stand time, p = 0.007; p = 0.009; p = 0.01, respectively). A linear regression model including four baseline kinematic features could significantly predict the motor outcome (p = 0.000214). Technology-based objective measures represent possible early and reproducible therapy-response and prognostic biomarkers.
Stroke impairs the control of isometric forces and muscle activations in the ipsilesional arm
Authors: Pellegrino Laura , Coscia Martina , Giannoni Psiche , Marinelli Lucio , Casadio Maura 
Published: September 2021

AbstractStroke often impairs the control of the contralesional arm, thus most survivors rely on the ipsilesional arm to perform daily living activities that require an efficient control of movements and forces. Whereas the ipsilesional arm is often called ‘unaffected’ or ‘unimpaired’, several studies suggested that during dynamic tasks its kinematics and joint torques are altered. Is stroke also affecting the ability of the ipsilesional arm to produce isometric force, as when pushing or pulling a handle? Here, we address this question by analyzing behavioral performance and muscles’ activity when subjects applied an isometric force of 10 N in eight coplanar directions. We found that stroke affected the ability to apply well-controlled isometric forces with the ipsilesional arm, although to a minor extent compared to the contralesional arm. The spinal maps, the analysis of single muscle activities and the organization of muscle synergies highlighted that this effect was mainly associated with abnormal activity of proximal muscles with respect to matched controls, especially when pushing or pulling in lateral directions.
Neurogenesis in the adult brain functionally contributes to the maintenance of chronic neuropathic pain
Authors: Tan Linette Liqi , Alfonso Julieta , Monyer Hannah , Kuner Rohini 
Published: September 2021

AbstractMaladaptive adult neurogenesis in the mammalian brain has been associated with diverse behaviors including disrupted learning, negative mood disorders and psychiatric conditions. However, its functional role in the generation and maintenance of chronic pathological pain has not yet been elucidated. Using an inducible genetic deletion in vivo mouse model, different behavioural paradigms and home cage monitoring systems, we show that an absence of adult neurogenesis does not impact the development of neuropathic injury-induced peripheral nociceptive hypersensitivity, but rather promotes the recovery of pathological pain as well as improves parameters associated with the state of well-being of the injured mice. These results provide a mechanistic insight into the mechanisms of chronic pain and implicate neurogenic processes as a potential therapeutic target for reducing pain and improving the quality of life for patients.
Shugoshin 2 is a biomarker for pathological grading and survival prediction in patients with gliomas
Authors: Kao Ying , Tsai Wen-Chiuan , Chen Ssu-Han , Hsu Shao-Yuan , Huang Li-Chun , Chang Chih-Ju , Huang Shih-Ming , Hueng Dueng-Yuan 
Published: September 2021

AbstractGlioblastomas are the most common type of adult primary brain neoplasms. Clinically, it is helpful to identify biomarkers to predict the survival of patients with gliomas due to its poor outcome. Shugoshin 2 (SGO2) is critical in cell division and cell cycle progression in eukaryotes. However, the association of SGO2 with pathological grading and survival in patients with gliomas remains unclear. We analyzed the association between SGO2 expression and clinical outcomes from Gene Expression Omnibus (GEO) dataset profiles, The Cancer Genome Atlas (TCGA), and Chinese Glioma Genome Atlas (CGGA). SGO2 mRNA and protein expression in normal brain tissue and glioma cell lines were investigated via quantitative RT-PCR, Western blot, and IHC staining. The roles of SGO2 in proliferation, migration, and apoptosis of GBM cells were studied with wound-healing assay, BrdU assay, cell cycle analysis, and JC-1 assay. The protein–protein interaction (PPI) was analyzed via Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). SGO2 mRNA expression predicted higher grade gliomas than non-tumor brain tissues. Kaplan–Meier survival analysis showed that patients with high-grade gliomas with a higher SGO2 expression had worse survival outcomes. SGO2 mRNA and protein expression were upper regulated in gliomas than in normal brain tissue. Inhibition of SGO2 suppressed cell proliferation and migration. Also, PPI result showed SGO2 to be a potential hub protein, which was related to the expression of AURKB and FOXM1. SGO2 expression positively correlates with WHO pathological grading and patient survival, suggesting that SGO2 is a biomarker that is predictive of disease progression in patients with gliomas.
Impact of cognitive reserve on dance intervention-induced changes in brain plasticity
Authors: Mitterová Kristína , Klobušiaková Patrícia , Šejnoha Minsterová Alžběta , Kropáčová Sylvie , Balážová Zuzana , Točík Jaroslav , Vaculíková Pavlína , Skotáková Alena , Grmela Roman , Rektorová Irena 
Published: September 2021

AbstractDance is a complex sensorimotor activity with positive effects on physical fitness, cognition, and brain plasticity in the aging population. We explored whether individual levels of cognitive reserve (CR) proxied by education moderate dance intervention (DI)-induced plasticity assessed by resting-state functional connectivity (rs-FC) changes of the sensorimotor network (SMN), and between the dorsal attention network (DAN) and anterior default mode network (aDMN). Our cohort consisted of 99 subjects, randomly assigned to either a DI group who underwent a 6-month intervention (n = 49, Mage = 69.02 ± 5.40) or a control group (n = 50, Mage = 69.37 ± 6.10). Moderation analyses revealed that CR moderated DI-induced increase of the SMN rs-FC with significant changes observed in participants with ≥ 15 years of education (b = 0.05, t(62) = 3.17, p = 0.002). Only DI alone was a significant predictor of the DAN–aDMN crosstalk change (b = 0.06, t(64) = 2.16, p = 0.035). The rs-FC increase in the SMN was correlated with an improved physical fitness measure, and changes in the DAN–aDMN connectivity were linked to better performance on figural fluency. Consistent with the passive CR hypothesis, we observed that CR correlated only with baseline behavioral scores, not their change.
Sensitive detection of Plasmodium vivax malaria by the rotating-crystal magneto-optical method in Thailand
Authors: Orbán Ágnes , Longley Rhea J. , Sripoorote Piyarat , Maneechai Nongnuj , Nguitragool Wang , Butykai Ádám , Mueller Ivo , Sattabongkot Jetsumon , Karl Stephan , Kézsmárki István 
Published: September 2021

AbstractThe rotating-crystal magneto-optical detection (RMOD) method has been developed for the rapid and quantitative diagnosis of malaria and tested systematically on various malaria infection models. Very recently, an extended field trial in a high-transmission region of Papua New Guinea demonstrated its great potential for detecting malaria infections, in particular Plasmodium vivax. In the present small-scale field test, carried out in a low-transmission area of Thailand, RMOD confirmed malaria in all samples found to be infected with Plasmodium vivax by microscopy, our reference method. Moreover, the magneto-optical signal for this sample set was typically 1–3 orders of magnitude higher than the cut-off value of RMOD determined on uninfected samples. Based on the serial dilution of the original patient samples, we expect that the method can detect Plasmodium vivax malaria in blood samples with parasite densities as low as $$\sim$$
∼
5–10 parasites per microliter, a limit around the pyrogenic threshold of the infection. In addition, by investigating the correlation between the magnitude of the magneto-optical signal, the parasite density and the erythrocytic stage distribution, we estimate the relative hemozoin production rates of the ring and the trophozoite stages of in vivo Plasmodium vivax infections.
Extracellular vesicles cargo from head and neck cancer cell lines disrupt dendritic cells function and match plasma microRNAs
Authors: de Paula Silva Elisangela , Marti Luciana Cavalheiro , Andreghetto Flávia Maziero , de Sales Romário Oliveira , Hoberman Martin , dos Santos Dias Bárbara , Diniz Larissa Figueiredo Alves , dos Santos Alessandro Marins , Moyses Raquel Ajub , Curioni Otávio Alberto , Lopez Rossana Veronica Mendoza , Nunes Fabio Daumas , Tajara Eloiza Helena , Severino Patricia 
Published: September 2021

AbstractExtracellular vesicles (EVs) are mediators of the immune system response. Encapsulated in EVs, microRNAs can be transferred between cancer and immune cells. To define the potential effects of EVs originated from squamous cell carcinoma cells on immune system response, we performed microRNA profiling of EVs released from two distinct cell lines and treated dendritic cells derived from circulating monocytes (mono-DCs) with these EVs. We confirmed the internalization of EVs by mono-DCs and the down-regulation of microRNA mRNA targets in treated mono-DCs. Differences in surface markers of dendritic cells cultivated in the presence of EVs indicated that their content disrupts the maturation process. Additionally, microRNAs known to interfere with dendritic cell function, and detected in EVs, matched microRNAs from squamous cell carcinoma patients’ plasma: miR-17-5p in oropharyngeal squamous cell carcinoma, miR-21 in oral squamous cell carcinoma, miR-16, miR-24, and miR-181a circulating in both oral and oropharyngeal squamous cell carcinoma, and miR-23b, which has not been previously described in plasma of head and neck squamous cell carcinoma, was found in plasma from patients with these cancer subtypes. This study contributes with insights on EVs in signaling between cancer and immune cells in squamous cell carcinoma of the head and neck.
Stabilizing nanolasers via polarization lifetime tuning
Authors: Roos Aycke , Meinecke Stefan , Lüdge Kathy 
Published: September 2021

AbstractWe investigate the emission dynamics of mutually coupled nanolasers and predict ways to optimize their stability, i.e., maximize their locking range. We find that tuning the cavity lifetime to the same order of magnitude as the dephasing time of the microscopic polarization yields optimal operation conditions, which allow for wider tuning ranges than usually observed in conventional semiconductor lasers. The lasers are modeled by Maxwell–Bloch type class-C equations. For our analysis, we analytically determine the steady state solutions, analyze the symmetries of the system and numerically characterize the emission dynamics via the underlying bifurcation structure. The polarization lifetime is found to be a crucial parameter, which impacts the observed dynamics in the parameter space spanned by frequency detuning, coupling strength and coupling phase.