bluuebunny/crossref_metadata_2025_split huggingface dataset:
Silent information regulator 2 promotes clear cell renal cell carcinoma progression through deacetylation and small ubiquitin‐related modifier 1 modification of glucose 6‐phosphate dehydrogenase
Authors: Ni Yueli , Yang Zhe , Agbana Yannick Luther , Bai Honggang , Wang Lianlin , Yang Lijuan , Yi Zihan , Cheng Jing , Zhang Qiao , Kuang Yingmin , Zhu Yuechun 
Published: July 2021

AbstractThe regulatory relationship between silent information regulator 2 (SIRT2) and glucose 6‐phosphate dehydrogenase (G6PD) in clear cell renal cell carcinoma (ccRCC) is still unclear. The present study aimed to explore the function of SIRT2 and its regulatory effect on G6PD in ccRCC. The Cancer Genome Atlas data mining of SIRT2 was first analyzed. Quantitative real‐time PCR and western blot analyses were used to assess the mRNA and protein expression levels, respectively. Cell viability, colony formation, cell cycle, cell apoptosis, and TUNEL assays and EdU staining were used to investigate the roles of SIRT2 in ccRCC proliferation and apoptosis. The coimmunoprecipitation (Co‐IP) assay was used to analyze the association between SIRT2 and G6PD in ccRCC cells. Quantitative Co‐IP assay was used to detect the levels of G6PD ubiquitination and small ubiquitin‐related modifier 1 (SUMO1). An in vivo experiment was also carried out to confirm in vitro findings. The results indicated that SIRT2 promoted ccRCC proliferation and inhibited apoptosis by regulating cell cycle and apoptosis related proteins. Silent information regulator 2 interacted with G6PD, facilitated its activity through deacetylation, and increased its stability by reducing its ubiquitination and enhancing its SUMO1 modification. Silent information regulator 2 also promoted ccRCC tumor development in vivo. Taken together, the present study indicated that SIRT2 promoted ccRCC progression by increasing G6PD activity and stability, and it could be a potential new diagnostic and therapeutic target for ccRCC.
Synthesis and anti‐diabetic activity of novel biphenylsulfonamides as glucagon receptor antagonists
Authors: Lee Chang‐Yong , Choi Hojung , Park Eun‐Young , Nguyen Thi‐Thao‐Linh , Maeng Han‐Joo , Mee Lee Kyoung , Jun Hee‐Sook , Shin Dongyun 
Published: July 2021

AbstractType 2 diabetes is characterized by chronic hyperglycemia. Insulin, a hormone secreted from pancreatic β‐cells, decreases blood glucose levels, and glucagon, a hormone secreted from pancreatic α‐cells, increases blood glucose levels by counterregulation of insulin through stimulation of hepatic glucose production. In diabetic patients, dysregulation of glucagon secretion contributes to hyperglycemia. Thus, inhibition of the glucagon receptor is one strategy for the treatment of hyperglycemia in type 2 diabetes. In this paper, we report a series of biphenylsulfonamide derivatives that were designed, synthesized, and then evaluated by cAMP and hepatic glucose production assays as glucagon receptor antagonists. Of these, compound 7aB‐3 decreased glucagon‐induced cAMP production and glucagon‐induced glucose production in the in vitro assays. Glucagon challenge tests and glucose tolerance tests showed that compound 7aB‐3 significantly inhibited glucagon‐induced glucose increases and improved glucose tolerance. These results suggest that compound 7aB‐3 has therapeutic potential for the treatment of type 2 diabetes.
Genetic spectrum of familial hypercholesterolemia and correlations with clinical expression: Implications for diagnosis improvement
Authors: Di Taranto Maria Donata , Giacobbe Carola , Palma Daniela , Iannuzzo Gabriella , Gentile Marco , Calcaterra Ilenia , Guardamagna Ornella , Auricchio Renata , Di Minno Matteo Nicola Dario , Fortunato Giuliana 
Published: July 2021

AbstractFamilial hypercholesterolemia (FH) is the most common genetic disease caused by variants in LDLR, APOB, PCSK9 genes; it is characterized by high levels of LDL‐cholesterol and premature cardiovascular disease. We aim to perform a retrospective analysis of a genetically screened population (528 unrelated patients—342 adults and 186 children) to evaluate the biochemical and clinical correlations with the different genetic statuses. Genetic screening was performed by traditional sequencing and some patients were re‐analyzed by next‐generation‐sequencing. Pathogenic variants, mainly missense in the LDLR gene, were identified in 402/528 patients (76.1%), including 4 homozygotes, 17 compound heterozygotes and 1 double heterozygotes. A gradual increase of LDL‐cholesterol was observed from patients without pathogenic variants to patients with a defective variant, to patients with a null variant and to patients with two variants. Six variants accounted for 51% of patients; a large variability of LDL‐cholesterol was observed among patients carrying the same variant. The frequency of pathogenic variants gradually increased from unlikely FH to definite FH, according to the Dutch Lipid Clinic Network criteria. Genetic diagnosis can help prognostic evaluation of FH patients, discriminating between the different genetic statuses or variant types. Clinical suspicion of FH should be considered even if few symptoms are present or if LDL‐cholesterol is only mildly increased.
Teacher violence, school satisfaction and subjective well‐being in children and adolescents in residential care: The moderation effect of staff support
Authors: Ortúzar Harry , Oriol Xavier , Miranda Rafael , Montserrat Carme 
Published: July 2021

AbstractThis study involved 608 children and adolescents between 7 and 18 years of age (Mage = 12.9, SDage = 2.70) from 47 residential care centres in Peru (RCC). The objective of the study was to observe the mediating effect of school satisfaction on the relationship between violence by teachers at school and the subjective well‐being of children and adolescents, considering how the low or high support from residential care staff can condition this mediating effect as well. The descriptive results show a very high prevalence of violence inflicted by teachers at school for both children and adolescents in residential care in Peru. Regarding the results obtained from the moderated mediation model results, the school satisfaction domain is observed to have a mediating effect on the relationship between teacher violence and subjective well‐being in children and adolescents. In addition, a moderated mediation effect conditioned by support from residential care staff is seen only in the case of children.
The Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC) burden of care study: Analysis of local treatments for lung metastases and systemic chemotherapy in 220 patients in the PulMiCC cohort
Authors: Treasure Tom , Farewell Vern , Macbeth Fergus , Batchelor Tim , Milosevic Misel , King Juliet , Zheng Yan , Leonard Pauline , Williams Norman R. , Brew‐Graves Chris , Morris Eva , Fallowfield Lesley ,   the PulMiCC investigators
Published: July 2021

AbstractAimThe aim of this work was to examine the burden of further treatments in patients with colorectal cancer following a decision about lung metastasectomy.MethodFive teams participating in the Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC) study provided details on subsequent local treatments for lung metastases, including the use of chemotherapy. For patients in three groups (no metastasectomy, one metastasectomy or multiple local interventions), baseline factors and selection criteria for additional treatments were examined.ResultsThe five teams recruited 220 patients between October 2010 and January 2017. No lung metastasectomy was performed in 51 patients, 114 patients had one metastasectomy and 55 patients had multiple local interventions. Selection for initial metastasectomy was associated with nonelevated carcinoembryonic antigen, fewer metastases and no prior liver metastasectomy. These patients also had better Eastern Cooperative Oncology Group scores and lung function at baseline. Four sites provided information on chemotherapy in 139 patients: 79 (57%) had one to five courses of chemotherapy, to a total of 179 courses. The patterns of survival after one or multiple metastasectomy interventions showed evidence of guarantee‐time bias contributing to an impression of benefit over no metastasectomy. After repeated metastasectomy, a significantly higher risk of death was observed, with no apparent reduction in chemotherapy usage.ConclusionRepeated metastasectomy is associated with a higher risk of death without reducing the use of chemotherapy. Continued monitoring without surgery might reassure patients with indolent disease or allow response assessment during systemic treatment. Overall, the carefully collected information from the PulMICC study provides no indication of an important survival benefit from metastasectomy.
Current research progress in targeted anti‐angiogenesis therapy for osteosarcoma
Authors: Liu Yun , Huang Nenggan , Liao Shijie , Rothzerg Emel , Yao Felix , Li Yihe , Wood David , Xu Jiake 
Published: July 2021

AbstractOsteosarcoma (OS) is the most common primary malignant bone tumour with a peak in incidence during adolescence. Delayed patient presentation and diagnosis is common with approximately 15% of OS patients presenting with metastatic disease at initial diagnosis. With the introduction of neoadjuvant chemotherapy in the 1970s, disease prognosis improved from 17% to 60%‐70% 5‐year survival, but outcomes have not significantly improved since then. Novel and innovative therapeutic strategies are urgently needed as an adjunct to conventional treatment modalities to improve outcomes for OS patients. Angiogenesis is crucial for tumour growth, metastasis and invasion, and its prevention will ultimately inhibit tumour growth and metastasis. Dysregulation of angiogenesis in bone microenvironment involving osteoblasts and osteoclasts might contribute to OS development. This review summarizes existing knowledge regarding pre‐clinical and developmental research of targeted anti‐angiogenic therapy for OS with the aim of highlighting the limitations associated with this application. Targeted anti‐angiogenic therapies include monoclonal antibody to VEGF (bevacizumab), tyrosine kinase inhibitors (Sorafenib, Apatinib, Pazopanib and Regorafenib) and human recombinant endostatin (Endostar). However, considering the safety and efficacy of these targeted anti‐angiogenesis therapies in clinical trials cannot be guaranteed at this point, further research is needed to completely understand and characterize targeted anti‐angiogenesis therapy in OS.
Acral multiple symmetrical palisaded encapsulated neuromas: A rare case report and review of the literature
Authors: Han Bing , Liu Hesong , Wang Hong 
Published: July 2021

AbstractPalisaded encapsulated neuroma (PEN) is a benign neoplasm composed of nerve tissue. It typically presents as isolated, asymptomatic, skin‐colored papules or nodules on the face, neck, or oral mucosa of the middle‐aged and elderly. Here, we reported a very unusual and unique case of acral multiple symmetrical PENs with no obvious systemic abnormalities and reviewed the published work on acral PEN.
Diversity–production relationships of fish communities in freshwater stream ecosystems
Authors: Myers Bonnie J. E. , Dolloff C. Andrew , Webster Jackson R. , Nislow Keith H. , Rypel Andrew L. 
Published: July 2021

AbstractAimEcological relationships between species richness and biomass production are increasingly thought to be pervasive across the globe. Yet, diversity–production relationships have not been explored extensively for freshwater fish communities even though fisheries production provides key services to humans. Our aim was to evaluate the diversity–production relationship of fish communities inhabiting freshwater streams across the Appalachian Mountain range and examine how diversity–production relationships varied across streams possessing different thermal signatures.LocationOur study area included 25 freshwater stream ecosystems spanning from Vermont to North Carolina in the United States. Twenty sites were located in Maryland south to Tennessee and North Carolina, while five additional higher latitude sites were sampled in Massachusetts and Vermont.MethodsWe sampled the 25 study streams from June to September 2012 and collected fish population information to calculate biomass, species richness, the Shannon diversity index and annual production for each fish community. Linear mixed effects models were used to analyse the relationship between diversity indices and total community production. We also compared diversity and production relationships across other taxa.ResultsAcross all streams, community fish production, biomass and P/B ratios ranged from 0.15–6.79 g m−2 y−1, 0.61–0.73 g m−2 and 0.21–1.07 y−1, respectively. Species richness had a significant positive effect (p = .012) on community fish production, while accounting for the thermal signature of the streams as a random effect and other habitat covariates. The Shannon diversity index did not have a significant effect (p = .101) on community production.Main conclusionsThe diversity–production relationship observed for stream fish communities was similar to other studies but demonstrated one of the highest slopes. Our results demonstrate that effects of biodiversity resonate to influence the production of fishes; thus, management of fisheries is more closely coupled to biodiversity than previously thought.
Severe mitral regurgitation recurrence after successful percutaneous mitral edge‐to‐edge repair by Mitraclip in primary mitral regurgitation: Insights from a three‐dimensional echocardiography study
Authors: Lavie‐Badie Yoan , Vannier Fabien , Cariou Eve , Fournier Pauline , Itier Romain , Cazalbou Stéphanie , Blanchard Virginie , Galinier Michel , Carrié Didier , Lairez Olivier , Bouisset Fréderic , Lhermusier Thibault 
Published: July 2021

AbstractBackgroundThe sustainability of the results of Mitraclip procedures is a source of concern.AimsTo investigate risk factors of severe mitral regurgitation (MR) recurrence after Mitraclip in primary MR.Methods and resultsEighty‐three patients undergoing successful Mitraclip procedures were retrospectively included. Valve anatomy and Mitraclips placement were comprehensively analyzed by post‐processing 3D echocardiographic acquisition. The primary composite endpoint was the recurrence of severe MR. The average age was 83±7 years‐old, 37 (44%) were female. Median follow‐up was 381 days (IQR 195–717) and 17 (20%) patients reached the primary endpoint. Main causes of recurrence of severe MR were relapse of a prolapse (64%) and single leaflet detachment (23%). Posterior coaptation line length (HR 1.06 95%CI 1.01–1.12 p = 0.02), poor imaging quality (HR 3.84, 95%CI 1.12–13.19; p = 0.03), and inter‐clip distance (HR 1.60, 95%CI 1.27–2.02; p < 0.01) were associated with the occurrence of the primary endpoint.ConclusionsRecurrence of severe MR after a MitraClip procedure for primary MR results from a complex interplay between anatomical (tissue excess) and procedural criteria (quality of ultrasound guidance and MitraClips spacing).
Host adaptation to novel pathogen introduction: Predicting conditions that promote evolutionary rescue
Authors: Golas Benjamin D. , Goodell Brandon , Webb Colleen T. 
Published: July 2021

AbstractNovel pathogen introduction can have drastic consequences for naive host populations, and outcomes can be difficult to predict. Evolutionary rescue (ER) provides a foundation for understanding whether hosts are driven to extinction or survive via adaptation. Currently, patterns of host population dynamics alongside evidence of adaptation are used to infer ER. However, the gap between established ER theory and complexity inherent in natural systems makes interpreting empirical patterns difficult because they can be confounded with ecological drivers of survival under current theory. To bridge this gap, we expand ER theory to include biological selective agents, such as pathogens. We find birth processes to be more important than previously theorised in determining ER potential. We employ a novel framework evaluating ER potential within natural systems and gain ability to identify system characteristics that make ER possible. Identifying these characteristics allows a shift from retrospective observation to a predictive mindset, and our findings suggest that ER occurrence may be more limited than previously thought. We use the plague system ofYersinia pestisinfectingCynomys ludovicianus(black‐tailed prairie dogs) andSpermophilus beecheyi(California ground squirrels) as a case study.
Optogenetic activation of the reticular nucleus of the thalamus attenuates limbic seizures via inhibition of the midline thalamus
Authors: Wicker Evan , Forcelli Patrick A. 
Published: July 2021

AbstractObjectiveThe nucleus reticularis of the thalamus (nRT) is most studied in epilepsy for its role in the genesis of absence seizures; much less is known regarding its role in other seizure types, including those originating in limbic structures and the temporal lobe. As it is a major source of inhibitory input to higher order thalamic nuclei, stimulation of the nRT may be an effective strategy to disrupt seizure activity that requires thalamic engagement.MethodsWe recorded single unit activity from the nRT prior to and after infusion of bicuculline into the area tempestas. We monitored single unit activity time‐locked with interictal spikes. We optogenetically activated the nRT in both the area tempestas and amygdala kindling models. We tested a role for projections from the nRT to higher order midline thalamic nuclei through the use of retrogradely trafficked viral vector.ResultsMean firing rate in the nRT was decreased after infusion of bicuculline into the area tempestas as compared to the preinfusion baseline. nRT unit firing in response to interictal spikes was heterogeneous, with an approximately equal proportion of neurons displaying (1) no change in firing, (2) increased firing, and (3) decreasing firing. Optogenetic activation of the nRT significantly suppressed seizure activity in both the area tempestas and amygdala kindling models. Optogenetic activation of contralaterally targeting projections but not ipsilaterally targeting projections from the nRT to the midline thalamus significantly suppressed seizures in the kindling model.SignificanceAlthough the nRT is typically thought of in the context of absence seizures, our data show that it may be a viable target for other seizure types. In two models that recapitulate the seizure types seen in temporal lobe epilepsy, nRT activation suppressed both electrographic and behavioral seizures. These data suggest that the nRT should be considered more broadly in the context of epilepsy.
Comorbidities in patients with epilepsy: Frequency, mechanisms and effects on long‐term outcome
Authors: Giussani Giorgia , Bianchi Elisa , Beretta Simone , Carone Davide , DiFrancesco Jacopo C. , Stabile Andrea , Zanchi Clara , Pirovano Marta , Trentini Claudia , Padovano Giada , Colombo Matteo , Cereda Diletta , Tinti Lorenzo , Scanziani Sofia , Gasparini Sara , Bogliun Graziella , Ferrarese Carlo , Beghi Ettore ,   PRO‐LONG Study Group
Published: July 2021

AbstractObjectiveTo assess frequency, types, and mechanisms of comorbidities in people with epilepsy and verify their association with disease features and outcome.MethodsThis cohort study was performed in 13 Italian epilepsy centers with nationwide distribution and accurate records. Eligible patients were children and adults diagnosed before December 31, 2005, and followed for a minimum of 10 years. Two pairs of raters independently reviewed patients’ records and classified each comorbidity. In case of disagreement, a third reviewer made the final decision. Comorbidities were classified according to type (organ/system) and underlying mechanism (causal, shared risk factors, chance association). Comorbidity types and mechanisms were described in the entire sample and according to epilepsy prognostic patterns (sustained remission, relapsing‐remitting course, no remission).ResultsOf 1006 included patients, 266 (26.4%) had at least one comorbidity. The most common were developmental/perinatal (7.5% of cases), psychiatric (6.2%), cardiovascular (5.3%), and endocrine/metabolic (3.8%). Among 408 reported comorbidities, the underlying mechanisms were, in decreasing order, chance association (42.2%), shared risk factors (31.1%), and causal (26.7%). Psychiatric diseases were present in 13.3% of patients with no remission, 5.9% of patients with relapsing‐remitting course, and 4.8% of patients with sustained remission (p = .016). The corresponding numbers for endocrine/metabolic diseases were respectively, 9.6%, 3.4%, and 2.9% (p = .013); for respiratory diseases were 3.6%, .3%, and .3% (p = .001), and for urogenital diseases were 3.6%, .7%, and 1.6% (p = .048). The association of endocrine/metabolic, psychiatric, and respiratory comorbidities with epilepsy prognosis was confirmed by multivariable analysis adjusted for the main demographic and clinical variables, with patients with these comorbidities showing a lower probability of achieving remission.SignificanceComorbidities in epilepsy are not uncommon and reflect differing underlying mechanisms. Psychiatric, endocrine/metabolic, and respiratory disorders are associated with a worse long‐term epileptological outcome.
Hyperpigmentation in a Chinese family with autosomal dominant Cole disease
Authors: Li Zhongtao , Wang Lin , Wang Sheng 
Published: July 2021

AbstractCole disease (OMIM 615522), caused by mutations in ENPP1, is a rare autosomal dominant or recessive genodermatosis characterized by guttate hypopigmentation and punctate palmoplantar keratoderma. To date, a few cases with autosomal recessive inheritance had been reported with hyperpigmentation. The aim of this case report was to investigate the molecular basis of individuals with hyperpigmentation, hypopigmentation and punctate keratoderma in a Chinese family. A Chinese pedigree of suspected Cole disease with hyperpigmentation was subjected to mutation detection in the ENPP1 gene. All exons of the ENPP1 gene and adjacent exon‐intron border sequences were amplified using polymerase chain reaction and directly sequenced. Three‐dimensional (3D) models of the wild‐type and mutated ENPP1 proteins were predicted by PyMOL viewer. Both of the proband and his affected father carried a heterozygous missense mutation p.C176R in ENPP1. In silico modelling of the ENPP1 wild‐type and ENPP1 with the p.C176R mutation showed the residue Arg‐176 disturbed the fold of the loop conformation. Based on clinical and genetic findings, a diagnosis of Cole disease was made. We identified a heterozygous mutation, p.C176R, in the ENPP1 gene in a Chinese family with Cole disease. This study clearly showed that hyperpigmentation could also occur in Cole disease in cases with autosomal dominant inheritance. Our data expand the phenotypic spectrum of ENPP1 mutations underlying Cole disease.
Toward sustainable production of value‐added bioenergy and industrial oils in oilseed and biomass feedstocks
Authors: Park Kiyoul , Sanjaya Sanju A. , Quach Truyen , Cahoon Edgar B. 
Published: July 2021

AbstractPlant fatty acids are used for food, feed, fuel, and industrial materials. Structurally and chemically diverse fatty acids, referred to as unusual or specialized fatty acids, are found in the seed oils of diverse plant species. Many unusual fatty acids have potential use as alternative and renewable sources of biofuels and bio‐based industrial feedstocks due to their variant structures' physical or functional properties. Oils enriched in these fatty acids can increase the value of oilseed crops and provide co‐products that can be readily extracted from lignocellulosic materials in biomass crops. Here, we describe recent progress in strategies for enhancement of oil production and quality in oilseed crops and the extension of this knowledge for metabolic engineering of biomass crops. Successful implementation of these strategies, in part, through the use of emerging synthetic biology tools, will provide added product value for the economic sustainability of biomass crops as bioenergy feedstocks.