bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pan‐HER inhibitors overcome lorlatinib resistance caused by NRG1/HER3 activation in ALK‐rearranged lung cancer
Authors: Taniguchi Hirokazu , Akagi Kazumasa , Dotsu Yosuke , Yamada Tadaaki , Ono Sawana , Imamura Erika , Gyotoku Hiroshi , Takemoto Shinnosuke , Yamaguchi Hiroyuki , Sen Triparna , Yano Seiji , Mukae Hiroshi 
Published: September 2022

AbstractLorlatinib, a third‐generation anaplastic lymphoma kinase (ALK)‐tyrosine kinase inhibitor (TKI) with a broad coverage against ALK mutations, has demonstrated dramatic effects in patients with ALK‐rearranged lung cancer. The mechanisms of acquired resistance to lorlatinib by secondary ALK compound mutations have recently been reported; however, resistance mechanisms other than secondary mutations remain unclear. Here, we investigated the molecular mechanisms of the acquired resistance in ALK‐rearranged lung cancer cells in vitro. We established two different lorlatinib‐resistant ALK‐rearranged lung cancer cell lines (H3122LR and A925LLR) via long‐term administration of lorlatinib. These resistant cells did not harbor the secondary ALK mutations and showed cross‐resistance to the other kinds of ALK‐TKIs (crizotinib or alectinib) compared with the parental cells; however, these resistant cells overexpressed the phosphorylated human epidermal growth factor receptor 3 (HER3) protein and the ligand of HER3 (neuregulin 1; NRG1). Pharmacological inhibition of HER3 with pan‐HER inhibitors or genetic knockdown of HER3 with siRNA resensitized H3122LR and A925LLR cells to lorlatinib in vitro, indicating that H3122LR and A925LLR acquired resistance by NRG1/HER3 activation. These findings demonstrated that targeting NRG1/HER3 is a potential novel therapeutic option for lorlatinib‐resistant ALK‐rearranged lung cancer.
Targeting the PTP1B‐Bcr‐Abl1 interaction for the degradation of T315I mutant Bcr‐Abl1 in chronic myeloid leukemia
Authors: Elgehama Ahmed , Wang Yixuan , Yu Ying , Zhou Lin , Chen Zhixiu , Wang Liwei , Sun Lijun , Gao Jian , Yu Biao , Shen Yan , Xu Qiang 
Published: September 2022

AbstractSmall‐molecule‐induced degradation of mutant Bcr‐Abl1 provides a potential approach to overcome Bcr‐Abl1 tyrosine kinase inhibitor (TKI)‐resistant chronic myeloid leukemia (CML). Our previous study reported that a synthetic steroidal glycoside SBF‐1 showed remarkable anti‐CML activity by inducing the degradation of native Bcr‐Abl1 protein. Here, we observed the comparable growth inhibition for SBF‐1 in CML cells harboring T315I mutant Bcr‐Abl1 in vitro and in vivo. SBF‐1 triggered its degradation through disrupting the interaction between protein‐tyrosine phosphatase 1B (PTP1B) and Bcr‐Abl1. Using SBF‐1 as a tool, we found that Tyr46 in the PTP1B catalytic domain and Tyr852 in the Bcr‐Abl1 pleckstrin‐homology (PH) domain are critical for their interaction. Moreover, the phosphorylation of Tyr1086 within the Bcr‐Abl1 SH2 domain recruited the E3 ubiquitin ligase c‐Cbl to catalyze K27‐linked ubiquitin chains, which serve as a recognition signal for p62‐dependent autophagic degradation. PTP1B dephosphorylated Bcr‐Abl1 at Tyr1086 and prevented the recruitment of c‐Cbl, leading to the stability of Bcr‐Abl1. This study unravels the action mechanism of PTP1B in stabilizing Bcr‐Abl1 protein and indicates that the PTP1B‐Bcr‐Abl1 interaction might be one of druggable targets for TKI‐resistant CML with point mutations.
A blockchain framework data integrity enhanced recommender system
Authors: Altulyan May , Yao Lina , Kanhere Salil , Huang Chaoran 
Published: September 2022

AbstractRecommender system for the IoT (RSIoT) has attracted considerable attention. By leveraging emerging technologies such as the Internet of Things (IoT), artificial intelligence, and blockchain, RSIoT improves various indicators of residents' life. However, data integrity threats may affect the accuracy and consistency of the data particularly in the IoT environment where most devices are inherently dynamic and have limited resources that could fail in ensuring the quality of data transmission. Prior work has focused on processing big data and ensuring their integrity by considering cloud storage service as the popular way. In this article, we address integrity of data leveraging blockchain capabilities to ensure the integrity of the critical data. We adapted the Ethereum blockchain to our RCS for ensuring integrity of data during sharing them between doctor and patient without handling their data by third party. We build four smart contracts that enable our system of gaining more advantage of blockchain. We evaluated the performance of our smart contracts in Kovan and Rinkeby test networks. The preliminary results show the feasibility and effectiveness of the proposed solution.
Using ecosystem services to identify inequitable outcomes in migratory species conservation
Authors: Chester Charles C. , Lien Aaron M. , Sundberg Juanita , Diffendorfer Jay E. , Gonzalez‐Duarte Columba , Mattsson Brady J. , Medellín Rodrigo A. , Semmens Darius J. , Thogmartin Wayne E. , Derbridge Jonathan J. , López‐Hoffman Laura 
Published: September 2022

AbstractBiodiversity conservation efforts have been criticized for generating inequitable socio‐economic outcomes. These equity challenges are largely analyzed as place‐based problems affecting local communities directly impacted by conservation programs. The conservation of migratory species extends this problem geographically since people in one place may benefit while those in another bear the costs of conservation. Thespatial subsidiesapproach offers an effective tool for analyzing such relationships between places connected by migratory species. Designed to quantify ecosystem services provided and received in specific locations across a migratory species’ range—and the disparities between them—the spatial subsidies approach highlights three axes of inequity: between indigenous and settler colonial societies, between urban and rural populations, and between the Global North and Global South. Recognizing these relationships is critical to achieving two mutually reinforcing policy goals: avoiding inequitable conservation outcomes in efforts to conserve migratory species, and ensuring effective long‐term conservation of migratory species. In demonstrating how the spatial subsidies approach enables the identification and quantification of inequities involving three migratory species (northern pintail ducks, monarch butterflies, and Mexican free‐tailed bats), we argue that a spatial subsidies approach could apply to migratory species conservation efforts worldwide under the context of “payments for ecosystem services.”
Letermovir for cytomegalovirus prophylaxis in high‐risk heart transplant recipients
Authors: Golob Stephanie , Batra Jaya , DeFilippis Ersilia M. , Uriel Matan , Carey Matt , Gaine Maureen , Mabasa Angelo , Fried Justin , Raikelkar Jayant , Restaino Susan , Hi Lee Sun , Latif Farhana , Yuzefpolskaya Melana , Colombo Paolo C. , Choe Jason , Majure David , Jennings Douglas , Pereira Marcus R. , Clerkin Kevin , Sayer Gabriel , Uriel Nir 
Published: September 2022

AbstractLetermovir is a novel agent for the prevention of cytomegalovirus (CMV) infection and disease that, unlike traditional CMV DNA polymerase inhibitors, does not carry the risk of myelosuppression. The purpose of this study was to evaluate the safety, efficacy, and clinical application of letermovir for CMV prophylaxis in heart transplant (HT) recipients. Between November 1, 2019, and October 1, 2021, at a single, tertiary care hospital, 17 HT recipients were initiated on letermovir due to leukopenia while on valganciclovir. Fifteen (88%) had high‐risk mismatch (CMV D+/R‐). Median time on letermovir was 5 months (interquartile range, 2–8 months.) At the end of the study period, nine of 17 patients (52.9%) were still on letermovir and four of the 17 (23.5%) had successfully completed the prophylaxis window on letermovir and been switched to the pre‐emptive strategy. One patient developed clinically significant CMV viremia in the setting of being unable to obtain medication due to insurance barriers but was later successfully restarted on letermovir. One patient was unable to tolerate letermovir due to symptoms of headache and myalgias. Two patients developed low‐level non‐clinically significant CMV viremia and were switched back to valacyclovir. All patients had tacrolimus dosages reduced at time of letermovir initiation to minimize the risk of supratherapeutic tacrolimus concentration. One patient required hospitalization due to symptomatic tacrolimus toxicity. For HT recipients who cannot tolerate valganciclovir, letermovir presents an alternative for CMV prophylaxis. Close monitoring for breakthrough CMV and calcineurin inhibitor levels is necessary. Larger studies are required to further delineate its use and help provide further evidence of its safety and efficacy.
Randomized controlled trial of EndoRings assisted colonoscopy versus standard colonoscopy
Authors: Thayalasekaran Sreedhari , Bhattacharyya Rupam , Chedgy Fergus , Basford Peter , Subramaniam Sharmila , Kandiah Kesavan , Thursby‐Pelham Fergus , Brown James , Alkandari Asma , Ellis Richard , Coda Sergio , Goggin Patrick , Amos Mark , Fogg Carole , Longcroft‐Wheaton Gaius , Bhandari Pradeep 
Published: September 2022

ObjectivesThe EndoRings device is a distal attachment consisting of two layers of circular flexible rings that evert mucosal folds. The aim of this study was to investigate whether EndoRing assisted colonoscopy (ER) improves polyp and adenoma detection compared to standard colonoscopy (SC).MethodsMulticenter, parallel group, randomized controlled trial.ResultsTotal of 556 patients randomized to ER (n = 275) or SC (n = 281). Colonoscopy completed in 532/556 (96%) cases. EndoRings removed in 74/275 (27%) patients. Total number of polyps in ER limb 582 vs. 515 in SC limb, P = 0.04. Total number of adenomas in ER limb 361 vs. 343 for SC limb, P = 0.49. A statistically significant difference in the mean number of polyps per patient in both the intention to treat (1.84 SC vs. 2.10 ER, P = 0.027) and per protocol (PP) (1.84 SC vs. 2.25 ER, P = 0.004).ConclusionsOur study shows promise for the EndoRings device to improve polyp detection.
Testing the migration syndrome: Comparative fecundity of migratory and non‐migratory nymphaline butterflies
Authors: Wiklund Christer , Friberg Magne 
Published: September 2022

AbstractEmpirical studies have shown a positive relationship between migration and fecundity, suggesting a ‘migration syndrome’ that also includes delayed reproduction and an extended reproductive lifespan. At the same time, life history theory predicts that the cost of migration should result in lower fecundity because both traits draw from a common resource.We test whether migration is associated with higher fecundity and delayed reproduction in five closely related butterfly species in the Nymphalini tribe. Two of these are migratory,Vanessa carduiandVanessa atalanta, and three are non‐migratory,Aglais urticae,Aglais io, andPolygonia c‐album, which appears in a diapausing and a non‐diapausing generation.Laboratory experiment of this study demonstrated a higher lifetime fecundity in the non‐migratory speciesA. urticaeandA. io, compared with the migratory species. When reproductive output was measured in terms of egg mass over adult female mass, also the non‐migratory speciesP. c‐albumhad a higher reproductive investment than the two migratory species, and the non‐diapausing generation had a higher reproductive output than the diapausing generation. All species butP. c‐albumdelayed reproduction until 5–7 days after eclosion/emergence.These results indicate that a migratory lifestyle carries a reproductive cost and suggests that the migratory habit has not resulted in selection for higher fecundity. However, the migratory species are highly fecund in a wider phylogenetic perspective, which leads to the conclusion that rather than selection having selected for high fecundity and delayed reproduction, these traits may be prerequisites for evolving a migratory lifestyle.
Occurrence of powdery mildew caused by Cystotheca kusanoi on Oak trees in China
Authors: Guan Guan‐Xiu , Liu Shu‐Yan , Murray Timothy D. , Tang Shu‐Rong 
Published: September 2022

AbstractQuercus spp. (Fagaceae) are evergreen and deciduous trees or shrubs, of which some are keystone species in forest ecosystems. Oak trees are common host plants of the powdery mildews within the genus Cystotheca. Cystotheca kusanoi, previously treated as heterotypic synonym of C. lanestris, was recently reinstated as a species of its own based on morphological re‐examinations and phylogenetic analyses of collections on Quercus spp. in Korea and Japan. The hyphal appressoria and presence or absence of fibrosin bodies in conidia of Cystotheca spp. was so far unclear. The present morphological examinations and phylogenetical analyses revealed that a fresh collection of powdery mildew on Q. spinosa from northwest China (Tibet Autonomous Region), and two herbarium specimens on Q. serrata from southwest China (Sichuan Province) and Q. variabilis from southeast China (Jiangsu Province) within re‐evaluated 12 herbarium specimens of C. lanestris s. lat. on Quercus spp. belong to C. kusanoi. To the best of our knowledge, this is the first report of C. kusanoi from China. Additionally, this is the first report of Q. spinosa as a host for C. kusanoi. Fibrosin bodies were not found in the fresh specimens of C. kusanoi. Nipple‐shaped to lobed hyphal appressoria have been observed and are described in the genus Cystotheca for the first time.
First report of Colletotrichum aeschynomenes causing anthracnose on Camellia oleifera in China
Authors: Li Lingling , Li He 
Published: September 2022

AbstractAnthracnose is a major disease of cultivated Camellia oleifera (tea‐oil tree) in China, with serious negative impacts on the yield and quality of cooking oil. In 2020, symptoms of anthracnose were observed on the leaves of tea‐oil trees in Hunan province, and Colletotrichum isolates were obtained from symptomatic leaf tissues. Morphological characterization and sequencing of ApMat gene region indicated that these isolates represented Colletotrichum aeschynomenes. Inoculation trial confirmed that C. aeschynomenes causes anthracnose on Ca. oleifera in China.
FENS‐Kavli Network of Excellence: Postponed, non‐competitive peer review for research funding
Authors: Dresler Martin 
Published: September 2022

AbstractReceiving research grants is among the highlights of an academic career, affirming previous accomplishments and enabling new research endeavours. Much of the process of acquiring research funding, however, belongs to the less favourite duties of many researchers: It is time consuming, often stressful and, in the majority of cases, unsuccessful. This resentment towards funding acquisition is backed up by empirical research: The current system to distribute research funding, via competitive calls for extensive research applications that undergo peer review, has repeatedly been shown to fail in its task to reliably rank proposals according to their merit, while at the same time being highly inefficient. The simplest, fairest and broadly supported alternative would be to distribute funding more equally across researchers, for example, by an increase of universities' base funding, thereby saving considerable time that can be spent on research instead. Here, I propose how to combine such a ‘funding flat rate’ model—or other efficient distribution strategies—with quality control through postponed, non‐competitive peer review using open science practices.
Task requirements affect the neural correlates of consciousness
Authors: Andersen Lau M. , Vinding Mikkel C. , Sandberg Kristian , Overgaard Morten 
Published: September 2022

AbstractIn the search for the neural correlates of consciousness, it is often assumed that there is a stable set within the relevant sensory modality. Within the visual modality, the debate has centred upon whether frontal or occipital activations are the best predictors of perceptual awareness. Although not accepted by all as definitive evidence, no‐report and decoding studies have indicated that occipital activity is the most consistently correlated with perceptual awareness whereas frontal activity might be closely related to aspects of cognition typically related to reports. However, perception is rarely just passive perceptionofsomething, but more or less always perceptionforsomething. That is, the task at hand for the perceiver may influence what is being perceived. This suggests an alternative view: that consciousness is not one specific ‘function’ that can be localized consistently to one area or event‐related component and that the specific attributes of the neural correlates of consciousness depend on the task at hand. To investigate whether and how tasks may influence the neural correlates of consciousness, we here contrasted two tasks, a perceptual task and a conceptual task, using identical stimuli in both tasks. Using magnetoencephalography, we found that the perceptual task recruited more occipital resources than the conceptual task. Furthermore, we found that between the two conditions, the amount of frontal resources recruited differed between different gradations of perceptual awareness partly in an unexpected manner. These findings support a view of task affecting the neural correlates of consciousness.
Genetic determinants of circulating metabolites and the risk of stroke and its subtypes
Authors: Wang Rong‐Ze , Huang Shu‐Yi , Li Hong‐Qi , Yang Yu‐Xiang , Chen Shi‐Dong , Yu Jin‐Tai 
Published: September 2022

AbstractBackground and purposeCirculating metabolites have been implicated in stroke pathogenesis, but their genetic determinants are understudied. Using a Mendelian randomization approach, our aim was to provide evidence for the relationship of circulating metabolites and the risk of stroke and its subtypes.MethodsGenetic instruments of 102 circulating metabolites were obtained from a genome‐wide association study, including 24,925 European individuals. Stroke was extracted from the MEGASTROKE dataset (67,162 cases; 454,450 controls) and a lacunar stroke dataset (7338 cases; 254,798 controls). The magnetic resonance imaging markers of cerebral small vessel disease and microstructural injury were evaluated by a genome‐wide association study of white matter hyperintensities (N = 18,381), fractional anisotropy (N = 17,663), mean diffusivity (N = 17,467) and brain microbleeds (N = 25,862). The inverse‐variance weighted method Mendelian randomization was used as the primary analytical method, and directional pleiotropy and heterogeneity were examined in sensitivity analyses.ResultsA genetic predisposition to a higher level of cholesterol in small and low‐density lipoprotein (LDL) was associated with risk of stroke (odds ratio [OR] 1.14, 95% confidence interval [CI] 1.08–1.21, p = 5.98 × 10−7), especially for large‐artery atherosclerotic stroke (OR 1.34, 95% CI 1.19–1.52, p = 1.90 × 10−6). Total lipids in LDL particles were also associated with risk of stroke. A genetically determined higher cholesterol level in high‐density lipoprotein (HDL‐C) was associated with risk of intracerebral haemorrhage (OR 1.74, 95% CI 1.23–2.45, p = 1.66 × 10−3). No statistically significant association was found between genetic predisposition to circulating metabolites and magnetic resonance imaging markers of cerebral small vessel disease and microstructural injury.ConclusionsGenetically determined levels of lipids in small LDL were associated with the risk of stroke, suggesting that a therapeutic strategy targeting small LDL levels may be crucial for stroke prevention. HDL‐C was positively associated with the risk of intracerebral haemorrhage.
Clinical features and reclassification of essential tremor with NOTCH2NLC GGC repeat expansions based on a long‐term follow‐up
Authors: Zhou Xun , Huang Hongyan , He Runcheng , Zeng Sheng , Liu Zhenhua , Xu Qian , Guo Jifeng , Yan Xinxiang , Duan Ranhui , Li Jinchen , Tang Beisha , Xu Yanming , Sun Qiying 
Published: September 2022

AbstractBackground and purposeNOTCH2NLC GGC repeat expansions have been identified to be associated with essential tremor (ET). Our aim was to characterize ET patients with NOTCH2NLC repeat expansions versus non‐expansions and describe distinctive clinical features of repeat expanded patients with long‐term follow‐up according to the new tremor classification.MethodsParticipants included 597 ET pedigrees, 412 sporadic cases and 1085 healthy controls. Repeat expansions of GGC in NOTCH2NLC were screened, and comprehensive clinical features were investigated. A longitudinal clinical assessment and reclassification were performed in NOTCH2NLC expanded patients.ResultsIn total, 27 ET pedigrees (27/597) and three sporadic patients (3/412) were identified with pathogenic NOTCH2NLC GGC repeat expansions (≥60 repeats). Intermediate‐length GGC repeats (41–59 repeats) were found in four sporadic ET cases and one control subject, and the frequency was higher than that in control participants (4/412 vs. 1/1085, p = 0.022). About 46 ET patients (43 familial cases from 27 pedigrees and three sporadic cases) with NOTCH2NLC GGC repeat expansions had higher Essential Tremor Rating Assessment Scale I, Essential Tremor Rating Assessment Scale II and Non‐Motor Symptoms Scale scores and lower Mini‐Mental State Examination scores than the patients without expansions. Patients with pathogenic GGC repeats were reclassified as pure ET (25/46), ET‐plus (11/46) and ET‐neuronal intranuclear inclusion disease (10/46) subgroups at 2–8 years of follow‐up.ConclusionOur results further supported that NOTCH2NLC GGC repeat expansions were associated with ET. Patients with pathogenic GGC repeats presented with more severe motor and non‐motor symptoms. Further long‐term follow‐up and subtype studies will help to define the role of NOTCH2NLC in ET.
Primary Sjögren syndrome‐related peripheral neuropathy: A systematic review and meta‐analysis
Authors: Liampas Andreas , Parperis Konstantinos , Erotocritou Maria Faidra , Nteveros Antonios , Papadopoulou Marianna , Moschovos Christos , Akil Mohammed , Coaccioli Stefano , Hadjigeorgiou Georgios M. , Hadjivassiliou Marios , Zis Panagiotis 
Published: September 2022

AbstractBackground and purposePrimary Sjögren syndrome (pSS) is a chronic, systemic, autoimmune disorder characterized by lymphocytic infiltrates of the exocrine organs, leading to sicca symptoms and parotid enlargement. pSS has been linked to various neurological manifestations, including peripheral neuropathy (PN). We aimed to provide a comprehensive analysis of the currently available evidence regarding pSS‐related PN.MethodsA literature search in the PubMed database was performed, and 49 papers were eligible to be included in this systematic review and meta‐analysis.ResultsThe pooled prevalence of PN in pSS is estimated to be 15.0% (95% confidence interval = 10.7%–20.7%). The mean age of pSS patients at PN diagnosis is 59 years. Among the patients with pSS and PN, 83% are females. Neuropathic symptoms usually precede or lead to the pSS diagnosis at a 2:1 ratio in patients with pSS‐related PN. The commonest type of pSS‐related PN is distal axonal polyneuropathy (80% of patients with pSS‐related PN), followed by sensory ganglionopathy. Peripheral and cranial mononeuropathies—particularly trigeminal—are also frequent. Risk factors for developing PN include increasing age and presence of vasculitis. Immune‐mediated pathogenetic mechanisms are discussed. Glucocorticoids are the most commonly used treatment option for managing pSS‐related PN, when associated with vasculitis, followed by the use of intravenous immunoglobulin.ConclusionsPN is very common in pSS patients. Evidence on long‐term prognosis of PN in pSS is limited, and further research is needed. Research into the use of immunosuppressive medication in nonvasculitic neuropathies in the context of pSS merits further consideration.