bluuebunny/crossref_metadata_2025_split huggingface dataset:
TASK‐1 channel blockade by AVE1231 increases vasocontractile responses and BP in 1‐ to 2‐week‐old but not adult rats
Authors: Shvetsova Anastasia A. , Gaynullina Dina K. , Schmidt Nadine , Bugert Peter , Lukoshkova Elena V. , Tarasova Olga S. , Schubert Rudolf 
Published: August 2020

Background and PurposeThe vasomotor role of K2P potassium channels during early postnatal development has never been investigated. We tested the hypothesis that TASK‐1 channel (K2P family member) contribution to arterial vascular tone and BP is higher in the early postnatal period than in adulthood.Experimental ApproachWe studied 10‐ to 15‐day‐old (“young”) and 2‐ to 3‐month‐old (“adult”) male rats performing digital PCR (dPCR) (using endothelium‐intact saphenous arteries), isometric myography, sharp microelectrode technique, quantitative PCR (qPCR) and Western blotting (using endothelium‐denuded saphenous arteries), and arterial pressure measurements under urethane anaesthesia.Key ResultsWe found mRNA of Kcnk1–Kcnk7, Kcnk12, and Kcnk13 genes to be expressed in rat saphenous artery, and Kcnk3 (TASK‐1) and Kcnk6 (TWIK‐2) were most abundant in both age groups. The TASK‐1 channel blocker AVE1231 (1 μmol·L−1) prominently depolarized arterial smooth muscle and increased basal tone level and contractile responses to methoxamine of arteries from young rats but had almost no effect in adult rats. The level of TASK‐1 mRNA and protein expression was higher in arteries from young compared with adult rats. Importantly, intravenous administration of AVE1231 (4 mg·kg−1) had no effect on mean arterial pressure in adult rats but prominently raised it in young rats.Conclusion and ImplicationsWe showed that TASK‐1 channels are important for negative feedback regulation of vasocontraction in young but not adult rats. The influence of TASK‐1 channels most likely contributes to low BP level at perinatal age.
Suppressor of Ty 16 promotes lung cancer malignancy and is negatively regulated by miR‐1227‐5p
Authors: Yang Lu , Wang Xing , Jiao Xinyan , Tian Bixia , Zhang Miao , Zhou Can , Wang Ruiqi , Chen He , Wang Bo , Li Juan , Liu Jie , Zhang Guanjun , Liu Peijun 
Published: August 2020

AbstractSuppressor of Ty 16 (Spt16) is a component of the facilitates chromatin transcription (FACT) complex, which is a histone chaperone and involved in gene transcription, DNA replication, and DNA repair. Previous studies showed that FACT is highly expressed in cancer, and cancer cells are more reliant on FACT than normal cells. However, the relationship between Spt16 and lung cancer remains unclear. In this study, we explored the functions of Spt16 in lung cancer cells. The effects of Spt16 on lung cancer cell proliferation, cell cycle progression, apoptosis, migration, and invasion were examined. We found that knockdown of Spt16 led to obvious decreases of both Rb and MCM7, and further activated the DNA damage response (DDR) pathway. In addition, a novel micro‐RNA, miR‐1227‐5p, directly targeted the 3′‐UTR of Spt16 and regulated the mRNA levels of Spt16. Furthermore, we found that CBL0137, the functional inhibitor of FACT, showed similar effects as loss of Spt16. Together, our data indicated that Spt16 is likely to be an essential regulator for lung cancer malignancy and is negatively regulated by miR‐1227‐5p.
Chaperone‐mediated autophagy receptor modulates tumor growth and chemoresistance in non–small cell lung cancer
Authors: Ichikawa Akihiro , Fujita Yu , Hosaka Yusuke , Kadota Tsukasa , Ito Akihiko , Yagishita Shigehiro , Watanabe Naoaki , Fujimoto Shota , Kawamoto Hironori , Saito Nayuta , Yoshida Masahiro , Hashimoto Mitsuo , Minagawa Shunsuke , Hara Hiromichi , Motoi Noriko , Yamamoto Yusuke , Ochiya Takahiro , Araya Jun , Kuwano Kazuyoshi 
Published: August 2020

AbstractChaperone‐mediated autophagy (CMA) is a lysosomal degradation pathway of selective soluble proteins. Lysosome‐associated membrane protein type 2a (LAMP2A) is the key receptor protein of CMA; downregulation of LAMP2A leads to CMA blockade. Although CMA activation has been involved in cancer growth, CMA status and functions in non–small cell lung cancer (NSCLC) by focusing on the roles in regulating chemosensitivity remain to be clarified. In this study, we found that LAMP2A expression is elevated in NSCLC cell lines and patient's tumors, conferring poor survival and platinum resistance in NSCLC patients. LAMP2A knockdown in NSCLC cells suppressed cell proliferation and colony formation and increased the sensitivity to chemotherapeutic drugs in vitro. Furthermore, we found that intrinsic apoptosis signaling is the mechanism of cell death involved with CMA blockade. Remarkably, LAMP2A knockdown repressed tumorigenicity and sensitized the tumors to cisplatin treatment in NSCLC‐bearing mice. Our discoveries suggest that LAMP2A is involved in the regulation of cancer malignant phenotypes and represents a promising new target against chemoresistant NSCLC.
Prognostic impact of CRTC1/3‐MAML2 fusions in salivary gland mucoepidermoid carcinoma: A multiinstitutional retrospective study
Authors: Okumura Yoshihide , Nakano Satsuki , Murase Takayuki , Ueda Kaori , Kawakita Daisuke , Nagao Toshitaka , Kusafuka Kimihide , Urano Makoto , Yamamoto Hidetaka , Kano Satoshi , Tsukahara Kiyoaki , Okami Kenji , Nagao Toru , Hanai Nobuhiro , Iwai Hiroshi , Kawata Ryo , Tada Yuichiro , Nibu Ken‐Ichi , Inagaki Hiroshi 
Published: August 2020

AbstractMucoepidermoid carcinoma (MEC) is rare, but the most common primary malignancy of the salivary gland and not infrequent in young individuals. CRTC1/3‐MAML2 fusions are frequently detected in MEC and are useful as a diagnostic biomarker. However, there has been debate as to whether the fusions have prognostic significance. In this study, we retrospectively collected 153 salivary gland MEC cases from 11 tertiary hospitals in Japan. As inclusion criteria, the MEC patients in this study had curative surgery as the initial treatment, received no preoperative treatment, and had no distant metastasis at the time of the initial surgery. The MEC diagnosis was validated by a central pathology review by five expert salivary gland pathologists. The CRTC1/3‐MAML2 fusions were detected using FISH and RT‐PCR. In 153 MEC cases, 90 (58.8%) were positive for CRTC1/3‐MAML2 fusions. During the follow‐up period, 28 (18.3%) patients showed tumor recurrence and 12 (7.8%) patients died. The presence of the fusions was associated with favorable tumor features. Of note, none of the fusion‐positive patients died during the follow‐up period. Statistical analysis showed that the presence of the fusions was a prognostic indicator of a better overall survival in the total and advanced‐stage MEC cohorts, but not in the early‐stage MEC cohort. In conclusion, CRTC1/3‐MAML2 fusions are an excellent biomarker for favorable overall survival of patients with salivary gland MEC.
A ceRNA network and a potential regulatory axis in gastric cancer with different degrees of immune cell infiltration
Authors: Zhang Kai , Zhang Lei , Mi Yang , Tang YouCai , Ren FeiFei , Liu Bin , Zhang Yi , Zheng PengYuan 
Published: August 2020

AbstractImmune cell infiltration is an important indicator of whether tumor patients will benefit from immunotherapy. Gastric cancer is one of the most common tumors in the world, and new indicators of immunotherapy are urgently needed. The aim of this study was to construct ceRNA networks in gastric cancer with different degrees of immune cell infiltration. We analyzed the expression profiles of different gastric cancer with different degrees of immune cell infiltration retrieved from The Cancer Genome Atlas (TCGA) database and found differentially expressed lncRNAs, mRNAs, and miRNAs. A ceRNA regulatory network of gastric cancer with different degrees of immune cell infiltration was constructed using functional annotation, RNA‐RNA interaction prediction, correlation analysis, survival analysis, and other comprehensive bioinformatics methods. The interaction and correlation between ceRNAs were verified using experiments on tumor tissues and cell lines. Cell line experiments showed a potential RP11‐1094M14.8/miR‐1269a/CXCL9 axis that was consistent with the ceRNA theory. qRT‐PCR results showed that RP11‐1094M14.8 knockdown significantly reduced the expression of CXCL9, and RP11‐1094M14.8 overexpression had the opposite effect. The results of clinical analysis of gastric cancer samples showed that RP11‐1094M14.8 and CXCL9 were highly expressed in hot tumors, and CXCL9 was positively correlated with a better prognosis for patients. The constructed novel ceRNA network and the potential regulatory axis may provide a comprehensive understanding of the potential mechanisms of development in gastric cancer with different degrees of immune cell infiltration. The RP11‐1094M14.8/miR‐1269a/CXCL9 axis may serve as a potential immune‐therapeutic target for gastric cancer with different degrees of immune cell infiltration.
Retinal microvasculature impairment in patients with congenital heart disease investigated by optical coherence tomography angiography
Authors: Li Cong , Zhong Pingting , Yuan Haiyun , Dong Xinran , Peng Qingsheng , Huang Manqing , Wu Qiaowei , Liu Baoyi , Xu Minghui , Kuang Yu , Zeng Xiaomin , Xiao Yu , Fang Ying , Yu Honghua , Yang Xiaohong 
Published: August 2020

AbstractImportanceA high prevalence of retinal abnormalities have been reported in congenital heart disease (CHD), but quantitative analysis of retinal vasculature is scarce. Optical coherence tomography angiography (OCTA) is a noninvasive method to quantitatively assess the retinal microvasculature.BackgroundTo investigate the retinal microvasculature changes in CHD patients by using OCTA.DesignCross‐sectional study.ParticipantsA total of 158 participants including 57 cyanotic CHD (CCHD) patients, 60 acyanotic CHD (ACHD) patients and 41 control subjects were included.MethodsAll participants underwent a comprehensive ophthalmologic examination, including refraction measurement, intraocular pressure measurement and OCTA.Main Outcome MeasuresVessel density (VD) was measured within the radial peripapillary capillary (RPC), superficial capillary plexus (SCP) and deep capillary plexus (DCP) of the macula.ResultsCCHD patients had significantly lower VD in the RPC, SCP and DCP (all P < .01) compared to control subjects, and significantly lower VD in the RPC and DCP (both P < .05) compared to ACHD patients. Besides, among the CHD group, VD in the RPC was positively correlated with oxygen saturation (whole image, ρ = 0.45; peripapillary, ρ = 0.48) and negatively correlated with haematocrit (whole image, ρ = 0.55; peripapillary, ρ = 0.55) (all P < .001).Conclusions and RelevanceRetinal VD might be a surrogate to reflect the effect of chronic systemic hypoxemia in CHD patients. OCTA could be a convenient and noninvasive tool to evaluate the retinal structure and function in CHD patients.
Sleep among youths in foster care: Associations with potentially traumatic events, PTSD and mental health
Authors: Lehmann Stine , Gärtner Askeland Kristin , Hysing Mari 
Published: August 2020

AbstractAmong maltreated youth in foster care, little is known about frequency of sleep problems and its association to potential traumatic events (PTEs) and mental health. Among youths in foster care, we examined: (1) sleep patterns, difficulties initiating and maintaining sleep (DIMS) and related functional impairment; (2) whether exposure to PTEs, symptoms of post‐traumatic stress disorder (PTSD) and general mental health problems are associated with DIMS and related functional impairment, controlling for age, gender and time in foster care; and (3) whether PTSD and general mental health problems mediate the association between PTEs and DIMS. Foster youths in Norway (n = 299) completed a survey on sleep behaviour, the Child and Adolescent Trauma Screen, and the Strengths and Difficulties Questionnaire. Overall, 53.2% reported DIMS. For 82.1%, these sleep problems had lasted 3 months plus. Increased PTEs, PTSD and general mental health problems were all associated with increased DIMS score. Increased rate of PTEs was associated with decreased sleep duration. PTSD and general mental health problems partially mediated the association between PTEs and DIMS. Youth in foster care are at high risk of sleep problems, related to traumatic experiences and mental health problems. Treatment of PTSD may improve sleep problems among maltreated youth.
Premature aging disorders: A clinical and genetic compendium
Authors: Schnabel Franziska , Kornak Uwe , Wollnik Bernd 
Published: August 2020

AbstractProgeroid disorders make up a heterogeneous group of very rare hereditary diseases characterized by clinical signs that often mimic physiological aging in a premature manner. Apart from Hutchinson‐Gilford progeria syndrome, one of the best‐investigated progeroid disorders, a wide spectrum of other premature aging phenotypes exist, which differ significantly in their clinical presentation and molecular pathogenesis. Next‐generation sequencing (NGS)‐based approaches have made it feasible to determine the molecular diagnosis in the early stages of a disease. Nevertheless, a broad clinical knowledge on these disorders and their associated symptoms is still fundamental for a comprehensive patient management and for the interpretation of variants of unknown significance from NGS data sets. This review provides a detailed overview on characteristic clinical features and underlying molecular genetics of well‐known as well as only recently identified premature aging disorders and also highlights novel findings towards future therapeutic options.
Spectrum and frequencies of non GJB2 gene mutations in Czech patients with early non‐syndromic hearing loss detected by gene panel NGS and whole‐exome sequencing
Authors: Safka Brozkova Dana , Poisson Marková Simona , Mészárosová Anna Uhrová , Jenčík Ján , Čejnová Vlasta , Čada Zdeněk , Laštůvková Jana , Rašková Dagmar , Seeman Pavel 
Published: August 2020

AbstractNon‐syndromic autosomal recessive hearing loss is an extremely heterogeneous disease caused by mutations in more than 80 genes. We examined Czech patients with early/prelingual non‐syndromic, presumably genetic hearing loss (NSHL) without known cause after GJB2 gene testing. Four hundred and twenty‐one unrelated patients were examined for STRC gene deletions with quantitative comparative fluorescent PCR (QCF PCR), 197 unrelated patients with next‐generation sequencing by custom‐designed NSHL gene panels and 19 patients with whole‐exome sequencing (WES). Combining all methods, we discovered the cause of the disease in 54 patients. The most frequent type of NSHL was DFNB16 (STRC), which was detected in 22 patients, almost half of the clarified patients. Other biallelic pathogenic mutations were detected in the genes: MYO15A, LOXHD1, TMPRSS3 (each gene was responsible for five clarified patients, CDH23 (four clarified patients), OTOG and OTOF (each gene was responsible for two clarified patients). Other genes (AIFM1, CABP2, DIAPH1, PTPRQ, RDX, SLC26A4, TBC1D24, TECTA, TMC1) that explained the cause of hearing impairment were further detected in only one patient for each gene. STRC gene mutations, mainly deletions remain the most frequent NSHL cause after mutations in the GJB2.
Vascular plant extinction in the continental United States and Canada
Authors: Knapp Wesley M. , Frances Anne , Noss Reed , Naczi Robert F. C. , Weakley Alan , Gann George D. , Baldwin Bruce G. , Miller James , McIntyre Patrick , Mishler Brent D. , Moore Gerry , Olmstead Richard G. , Strong Anna , Kennedy Kathryn , Heidel Bonnie , Gluesenkamp Daniel 
Published: August 2020

AbstractExtinction rates are expected to increase during the Anthropocene. Current extinction rates of plants and many animals remain unknown. We quantified extinctions among the vascular flora of the continental United States and Canada since European settlement. We compiled data on apparently extinct species by querying plant conservation databases, searching the literature, and vetting the resulting list with botanical experts. Because taxonomic opinion varies widely, we developed an index of taxonomic uncertainty (ITU). The ITU ranges from A to F, with A indicating unanimous taxonomic recognition and F indicating taxonomic recognition by only a single author. The ITU allowed us to rigorously evaluate extinction rates. Our data suggest that 51 species and 14 infraspecific taxa, representing 33 families and 49 genera of vascular plants, have become extinct in our study area since European settlement. Seven of these taxa exist in cultivation but are extinct in the wild. Most extinctions occurred in the west, but this outcome may reflect the timing of botanical exploration relative to settlement. Sixty‐four percent of extinct plants were single‐site endemics, and many occurred outside recognized biodiversity hotspots. Given the paucity of plant surveys in many areas, particularly prior to European settlement, the actual extinction rate of vascular plants is undoubtedly much higher than indicated here.
Viability testing of discarded livers with normothermic machine perfusion: Alleviating the organ shortage outweighs the cost
Authors: Raigani Siavash , De Vries Reinier J. , Carroll Cailah , Chen Ya‐Wen , Chang David C. , Shroff Stuti G. , Uygun Korkut , Yeh Heidi 
Published: August 2020

AbstractBackgroundOver 700 donor livers are discarded annually in the United States due to high risk of poor graft function. The objective of this study was to determine the impact of using normothermic machine perfusion to identify transplantable livers among those currently discarded.Study DesignA series of 21 discarded human livers underwent viability assessment during normothermic machine perfusion. Cross‐sectional analysis of the Scientific Registry of Transplant Recipients database and cost analysis was performed to extrapolate the case series to national experience.Results21 discarded human livers were included in the perfusion cohort. 11 of 20 (55%) eligible grafts met viability criteria for transplantation. Grafts in the perfusion cohort had a similar donor risk index compared with discarded grafts (n = 1402) outside of New England in 2017 and 2018 (median [IQR]: 2.0 [1.5, 2.4] vs. 2.0 [1.7, 2.3],P = .40). 705 (IQR 677‐741) livers were discarded annually in the United States since 2005, translating to the potential for 398 additional transplants nationally. The median cost to identify a transplantable graft with machine perfusion was $28,099 USD.ConclusionsNormothermic machine perfusion of discarded livers could identify a significant number of transplantable grafts, significantly improving access to liver transplantation.
Multi‐site Investigation of Genetic Determinants of Warfarin Dose Variability in Latinos
Authors: El Rouby Nihal , Rodrigues Marcatto Leiliane , Claudio Karla , Camargo Tavares Letícia , Steiner Heidi , Botton Marianna R. , Lubitz Steve A. , Fallon Echo N. , Yee Kevin , Kaye Justin , Scott Stuart A. , Karnes Jason , Caleb Junior de Lima Santos Paulo , Duconge Jorge , Cavallari Larisa H. 
Published: August 2020

We conducted a multi‐site investigation of genetic determinants of warfarin dose variability in Latinos from the U.S. and Brazil. Patients from four institutions in the United States (n = 411) and Brazil (n = 663) were genotyped for VKORC1 c.‐1639G> A, common CYP2C9 variants, CYP4F2*3, and NQO1*2. Multiple regression analysis was used in the U.S. cohort to test the association between warfarin dose and genotype, adjusting for clinical factors, with further testing in an independent cohort of Brazilians. In the U.S. cohort, VKORC1 and CYP2C9 variants were associated with lower warfarin dose (β = −0.29, P < 2.0 × 10−16; β = −0.21, P = 4.7 × 10−7, respectively) whereas CYP4F2 and NQO1 variants were associated with higher dose (β = 0.10, P = 2 × 10−4; β = 0.10, P = 0.01, respectively). Associations with VKORC1 (β = −0.14, P = 2.0 × 10−16), CYP2C9 (β = −0.07, P = 5.6 × 10−10), and CYP4F2 (β = 0.03, P = 3 × 10−3), but not NQO1*2 (β = 0.01, P = 0.30), were replicated in the Brazilians, explaining 43–46% of warfarin dose variability among the cohorts from the U.S. and Brazil, respectively. We identified genetic associations with warfarin dose requirements in the largest cohort of ancestrally diverse, warfarin‐treated Latinos from the United States and Brazil to date. We confirmed the association of variants in VKORC1, CYP2C9, and CYP4F2 with warfarin dose in Latinos from the United States and Brazil.
Pseudoaneurysm of the mitral‐aortic intervalvular fibrosa following endocarditis and aortic valve surgery in an infant—Case report and exhaustive systematic review of pediatric cases
Authors: Ahmed Aziez , Shivaram Pushpa , Zakaria Dala 
Published: August 2020

AbstractPseudoaneurysm of the mitral‐aortic intervalvular fibrosa (P‐MAIVF) continues to be a rare diagnosis in children. Etiology, presentation, and management strategies are considerably different from adults. We report a fatal case of P‐MAIVF with classical transthoracic and transesophageal echocardiographic findings complemented by CT imaging. The natural course of uncomplicated/asymptomatic P‐MAIVF is largely unknown since most patients are offered surgery. We present an extensive literature review of pediatric P‐MAIVF and highlight important differences from the adult form of this disease.
Safety and feasibility of transesophageal echocardiography in patients with prior esophageal surgery
Authors: Smith Bradford B. , Rehfeldt Kent H. , Meinhardt James R. , Smith Mark M. 
Published: August 2020

AbstractBackgroundTransesophageal echocardiography (TEE) is a specialized form of cardiac ultrasound and has been associated with rare but serious complications. In patients with prior esophageal surgery, the risk of esophageal damage or the inability to perform a comprehensive and successful TEE warrants further evaluation.MethodsRetrospective study of patients with prior esophageal surgery who underwent TEE between June 21, 2002 and October 15, 2019. Medical and echocardiographic records were reviewed for image quality and procedural complications. Post‐procedure complications and 30‐day all‐cause mortality were collected. Evaluation by gastroenterology (GI), otolaryngology/ear, nose, throat (ENT), or thoracic surgery (TS) within 30 days of TEE was reviewed in detail.ResultsNinety‐five patients with prior esophageal surgery underwent 145 TEEs. The most commonly performed esophageal procedures were anti‐reflux operations (89%). TEE image quality was degraded in 16% while transgastric imaging was not completed in 37% of cases. A comprehensive TEE was completed in 57% of patients with diagnostic study goals achieved in 96% of cases. Comments describing procedural difficulty were reported in 6% while comments on procedural complications occurred in 1% of cases. Post‐procedure complications occurred in 1% of patients including hypotension and unplanned hospital/ICU admission.ConclusionsConcern for esophageal damage and the inability to perform a comprehensive and diagnostic TEE may limit the usefulness of TEE in patients with prior esophageal surgery. While TEE‐associated complications were rare in this series, a conservative approach with a thorough pre‐procedure assessment, including multi‐disciplinary evaluation when appropriate, is prudent in this complex cohort of patients.