bluuebunny/crossref_metadata_2025_split huggingface dataset:
“On‐Water” Palladium‐Catalyzed Tandem Cyclization Reaction for the Synthesis of Biologically Relevant 4‐Arylquinazolines
Authors: Yuan Shuo , Yu Bin , Liu Hong‐Min 
Published: August 2019

AbstractThe quinazoline scaffold is prevalent in pharmaceutically relevant molecules that show diverse biological activities. Herein, we report an efficient “on‐water” palladium‐catalyzed tandem cyclization reaction from commercially available arylboronic acids and benzonitriles that enable the rapid access to 4‐arylquinazoline scaffolds in good to excellent yields (45 examples, up to 98 % yield). This protocol has shown good functional group tolerance and broad substrate scope. The reaction was also performed on a gram scale and successfully applied to the synthesis of the highly potent and selective PI3Kδ inhibitor N11, showing the practicability and synthetic utility of the protocol. In this reaction, the quinazoline scaffold is efficiently constructed with the simultaneous formation of one C−C bond and one C−N bond. Collectively, the protocol could serve as an alternative strategy to synthesize biologically important quinazoline scaffolds.
Direct Dimesitylborylation of Benzofuran Derivatives by an Iridium‐Catalyzed C−H Activation with Silyldimesitylborane
Authors: Shishido Ryosuke , Sasaki Ikuo , Seki Tomohiro , Ishiyama Tatsuo , Ito Hajime 
Published: August 2019

AbstractDirect dimesitylborylation of benzofuran derivatives by a C−H activation catalyzed by an iridium(I)/N‐heterocyclic carbene (NHC) complex in the presence of Ph2MeSi‐BMes2 afforded the corresponding dimesitylborylation products in good to high yield with excellent regioselectivity. This method provides a straightforward route to donor–(π‐spacer)–acceptor systems with intriguing solvatochromic luminescence properties.
Electrospun Cu‐Deposited Flexible Fibers as an Efficient Oxygen Evolution Reaction Electrocatalyst
Authors: Morinaga Asuka , Tsutsumi Hiromori , Katayama Yu 
Published: August 2019

AbstractDeveloping oxygen evolution reaction (OER) catalysts with high activity, long‐term durability, and at low cost remains a great challenge. Herein, we report the high activity of fibrous Cu‐based catalysts. The synthesis process is simple and scalable. Electrospinning method was selected to synthesize fibrous polymer substrates (Poly(vinylidene fluoride‐co‐hexafluoropropylene, PVdF‐HFP), which are then covered by Cu via electroless deposition. Cu‐deposited PVdF‐HFP with different microstructures having smooth and roughened surfaces were also synthesized by drop‐casting and impregnation method, respectively, to emphasize the importance of the microstructures on OER activity. The OER activity and durability were studied by linear sweep voltammetry, chronoamperometry, and Tafel slope analysis. The Cu/PVdF‐HFP fibrous catalysts exhibit significantly improved OER activity and durability compared with Cu plate as well as Cu‐deposited PVdF‐HFP with different microstructures. The unique fibrous structure provides better mass transport, diffusion, and large active surface area. In addition to the advantages of the fibrous structure, attenuated total reflection infrared (ATR‐IR) and ex situ X‐ray photoelectron spectroscopy revealed that the improved specific activity for Cu/PVdF‐HFP fiber can be attributed to the synergistic effect between Cu and Cu/PVdF‐HFP (electron transfer from Cu to PVdF‐HFP) at the Cu|PVdF‐HFP interface, which results in optimized reaction energetics for the OER.
Impact of Hepatic Steatosis on Resting Metabolic Rate and Metabolic Adaptation in Response to Intentional Weight Loss
Authors: Rachakonda Vikrant P. , DeLany James P. , Kershaw Erin E. , Behari Jaideep 
Published: August 2019

Weight loss is the primary intervention for nonalcoholic fatty liver disease (NAFLD). A decrease in resting metabolic rate (RMR) out of proportion to the degree of weight loss may promote weight regain. We aimed to determine the impact of hepatic steatosis on weight loss‐associated changes in RMR and metabolic adaptation, defined as the difference between predicted and measured RMR after weight loss. We retrospectively analyzed prospectively collected data from 114 subjects without diabetes (52 with NAFLD), with body mass index (BMI) >35, and who enrolled in a 6‐month weight loss intervention. Hepatic steatosis was determined by unenhanced computed tomography scans by liver:spleen attenuation ratio <1.1. RMR was measured by indirect calorimetry. At baseline, patients with hepatic steatosis had higher BMI, fat mass (FM), fat‐free mass (FFM), and RMR (RMR, 1,933 kcal/day; 95% confidence interval [CI], 841‐2,025 kcal/day; versus 1,696; 95% CI, 1,641‐1,751; P < 0.0001). After 6 months, the NAFLD group experienced larger absolute declines in weight, FM, and FFM, but percentage changes in weight, FFM, and FM were similar between groups. A greater decline in RMR was observed in patients with NAFLD (−179 kcal/day; 95% CI, −233 to −126 kcal/day; versus −100; 95% CI, −51 to −150; P = 0.0154) for the time × group interaction, and patients with NAFLD experienced greater metabolic adaptation to weight loss (−97 kcal/day; 95% CI, −143 to −50 kcal/day; versus −31.7; 95% CI, −74 to 11; P = 0.0218) for the prediction × group interaction. The change (Δ) in RMR was significantly associated with ΔFM, ΔFFM, and baseline RMR, while metabolic adaptation was significantly associated with female sex and ΔFM only. Conclusion: Hepatic steatosis is associated with a greater reduction in FM, which predicts RMR decline and a higher metabolic adaptation after weight loss, potentially increasing the risk of long‐term weight regain.
Investigating the effect of custom‐made insoles and exercises on lower limb and back discomfort in assembly‐line workers in a rubber tire factory: A randomized controlled trial
Authors: Mousavi Elahe , Zamanian Zahra , Hadadi Mohammad , Sobhani Sobhan 
Published: August 2019

AbstractMany occupations require standing for prolonged periods, which can be a major contributor to musculoskeletal problems and cause disturbances in different parts of the body, especially the lower back and lower extremities. The aim of this study was to investigate the effect of custom‐made insoles and exercise training on the lower limb and lower back discomfort in workers on a production line at a rubber tire factory. One hundred male workers (mean age 35.96 years, work experience of 10.62 years, standing time 6.58 hr) participated in this randomized controlled trial. The men were randomly assigned to one of four groups: (a) custom‐made insole plus lower limb exercises, (b) insoles only, (c) lower limb exercises only, and (d) no intervention. Discomfort level was recorded with a visual analog scale and a body map. The data were analyzed with analysis of covariance. The results showed a significant difference in discomfort levels between groups in the lower back (p = .001), thigh (p = .001), and knee (p = .001) areas. The combined insole and exercise group had less discomfort in the lower back, thigh, and knee. In the group that used the insole only without exercises, the discomfort level in the lower back area was reduced. The results indicate that the simultaneous use of insoles and exercises might be an effective intervention to reduce discomfort in the lower limbs and lower back in workers who remain standing for prolonged periods.
Model‐Based Product Line Engineering to Plan and Track Submarine Configuration
Authors: Hause Matthew , Hallett Jon 
Published: August 2019

ABSTRACTOne can measure the life of a class of submarines in decades. As such, the operational demands and expectations change both strategically and tactically over its lifetime. Coupling this adaptability with the length of time submarines take to design, build, and maintain, no two as‐built submarines in a class will ever be the same, even when constructed/maintained to the same build‐to design. Traditionally, we have accepted this as the standard, and in most cases the configuration management team managed the full information set at a class or batch level, but not at an individual submarine level. The team managed the configuration of an individual submarine in terms of agreed changes against the class or batch baseline. Advances in technology (hardware performance, software tools, and standards) now give us the opportunity to not only manage the full information set related to individual submarine system configuration baselines as they change over time, but also undertake rigorous model‐based trade‐off studies to plan the manner in which we can modify a class, a batch, an individual submarine (variant), or any combination thereof over time. This paper will explore the use of model‐based systems engineering (MBSE) coupled with recent developments of product line engineering (PLE)/orthogonal variability modelling (OVM) to provide a means to plan, track, manage, and evaluate an individual submarine's configuration over time in the context of the class, whilst simultaneously highlighting the wider application in the submarine enterprise and beyond.
Retracted: Silencing of keratin 1 inactivates the Notch signaling pathway to inhibit renal interstitial fibrosis and glomerular sclerosis in uremia
Authors: Chen Wen , Wang Zhi‐Kui , Ren Yue‐Qin , Zhang Lei , Sun Li‐Na , Man Yu‐Lin , Zhou Zhong‐Qi 
Published: August 2019

AbstractRenal interstitial fibrosis is a key factor in the development of chronic renal diseases, possibly leading to uremia. The present study conducted aimed to assess the hypothesis whether keratin 1 (KRT1) silencing could suppress kidney interstitial fibrosis and glomerular sclerosis via the Notch pathway to alleviate uremic symptoms. Differentially expressed genes associated with uremia were identified using the gene expression omnibus (GEO) database. Uremic rat models were established, in which short hairpin‐RNA against KRT1, activators, and inhibitors of the Notch pathway were transfected. To further validate the mechanism of KRT1 in uremia, KRT1 expression, cell apoptosis, glomerular area (GA), and glomerular capillary volume (GV), the score of glomerular sclerosis, and tubulointerstitial injury were assayed and investigated. GEO database revealed that KRT1 was upregulated in uremia and regulated the Notch pathway. GA, GV, cell apoptosis, glomerular sclerosis, and tubulointerstitial injury were typically located in more elevated levels of uremia in rats. KRT1 silencing and Notch pathway inhibition decreased the expression of Jagged1, Notch1, NICD1, Hey1, Hes1, α‐SMA, and FN, which further resulted in decreased cell apoptosis, GA, GV, the score of glomerular sclerosis, and tubulointerstitial injury. Subsequently, the effect of KRT1 silencing on uremia was no longer evident once the Notch pathway was activated. The co‐localization of high expression KRT1 and Notch1 was found in uremia. In summary, the results identified KRT1 as a key regulator in uremia progression, and KRT1 silencing can suppress glomerular sclerosis and tubulointerstitial injury via inactivation of the Notch pathway in uremic rats.
RETRACTED: Silencing of tumor‐suppressive NR_023387 in renal cell carcinoma via promoter hypermethylation and HNF4A deficiency
Authors: Zhou Hui , Guo Liang , Yao Weimin , Shi Runlin , Yu Gan , Xu Hua , Ye Zhangqun 
Published: August 2019

AbstractDysregulation of the epigenetic status of long noncoding RNAs (lncRNAs) has been linked to diverse human diseases including human cancers. However, the landscape of the whole‐genome methylation profile of lncRNAs and the precise roles of these lncRNAs remain elusive in renal cell carcinoma (RCC). We first examined lncRNA expression profiles in RCC tissues and corresponding adjacent normal tissues (NTs) to identify the lncRNA signature of RCC, then lncRNA Promoter Microarray was performed to depict the whole‐genome methylation profile of lncRNAs in RCC. Combined analysis of the lncRNAs expression profiles and lncRNAs Promoter Microarray identified a series of downregulated lncRNAs with hypermethylated promoter regions, including NR_023387. Quantitative real‐time polymerase chain reaction (RT‐PCR) implied that NR_023387 was significantly downregulated in RCC tissues and cell lines, and lower expression of NR_023387 was correlated with shorter overall survival. Methylation‐specific PCR, MassARRAY, and demethylation drug treatment indicated that hypermethylation in the NR_023387 promoter contributed to its silencing in RCC. Besides, HNF4A regulated the expression of NR_023387 via transcriptional activation. Functional experiments demonstrated NR_023387 exerted tumor‐suppressive roles in RCC via suppressing the proliferation, migration, invasion, tumor growth, and metastasis of RCC. Furthermore, we identified MGP as a putative downstream molecule of NR_023387, which promoted the epithelial–mesenchymal transition of RCC cells. Our study provides the first whole‐genome lncRNA methylation profile in RCC. Our combined analysis identifies a tumor‐suppressive and prognosis‐related lncRNA NR_023387, which is silenced in RCC via promoter hypermethylation and HNF4A deficiency, and may exert its tumor‐suppressive roles by downregulating the oncogenic MGP.
Association between DIO2 polymorphism and the risk of Kashin–Beck disease in the Tibetan population
Authors: Jin Tianbo , Wang Li , He Xue , Liu Ming , Bai Mei , Rong Hao , He Yongjun , Yuan Dongya 
Published: August 2019

AbstractBackgroundKashin–Beck disease (KBD) is a local, multiple and deformable osteoarthropathy, mostly occurring in Tibet. Type 2 iodothyronine deiodinase (DIO2) is implicated in the activation of thyroid hormones to which the bones are very sensitive. Therefore, it is necessary to explore the association between KBD and DIO2 in the Tibetan population.MethodsWe carried out a case–control study among 316 cases and 320 controls from a Tibetan population. Seven single nucleotide polymorphisms in DIO2 were selected and genotyped using the Agena MassARRAY platform (Agena Bioscience, San Diego, CA, USA). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression analysis. HaploReg (https://pubs.broadinstitute.org/mammals/haploreg/haploreg.php) and GTEx (http://www.gtexportal.org) databases were applied for functional assessment of the polymorphisms.ResultsThe “A/C" genotype of rs1352815 (OR = 3.18, 95% CI = 1.14–8.85, p = 0.027) and the “A/G" genotype of rs1388382 (OR = 3.80, 95% CI = 1.30–11.11, p = 0.015) were associated with the susceptibility of KBD under the co‐dominant model. With gender stratification analysis, rs1388382 showed obvious evidence for correlation with an elevated risk of KBD in females under the co‐dominant model (OR = 3.32, 95% CI = 1.06–10.41, p = 0.039).ConclusionsThe results obtained in the present study indicate that DIO2 polymorphisms rs1352815 and rs1388382 were correlated with KBD susceptibility among Tibetans, which also sheds new light on the role of DIO2 in the development of KBD.
History of scoria‐cone eruptions on the eastern shoulder of the Kenya–Tanzania Rift revealed in the 250‐ka sediment record of Lake Chala near Mount Kilimanjaro
Authors: Martin‐Jones Catherine , Lane Christine , Van Daele Maarten , Meeren Thijs Van Der , Wolff Christian , Moorhouse Heather , Tomlinson Emma , Verschuren Dirk 
Published: August 2019

ABSTRACTReconstructions of the timing and frequency of past eruptions are important to assess the propensity for future volcanic activity, yet in volcanic areas such as the East African Rift only piecemeal eruption histories exist. Understanding the volcanic history of scoria‐cone fields, where eruptions are often infrequent and deposits strongly weathered, is particularly challenging. Here we reconstruct a history of volcanism from scoria cones situated along the eastern shoulders of the Kenya–Tanzania Rift, using a sequence of tephra (volcanic ash) layers preserved in the ~250‐ka sediment record of Lake Chala near Mount Kilimanjaro. Seven visible and two non‐visible (crypto‐) tephra layers in the Lake Chala sequence are attributed to activity from the Mt Kilimanjaro (northern Tanzania) and the Chyulu Hills (southern Kenya) volcanic fields, on the basis of their glass chemistry, textural characteristics and known eruption chronology. The Lake Chala record of eruptions from scoria cones in the Chyulu Hills volcanic field confirms geological and historical evidence of its recent activity, and provides first‐order age estimates for seven previously unknown eruptions. Long and well‐resolved sedimentary records such as that of Lake Chala have significant potential for resolving regional eruption chronologies spanning hundreds of thousands of years.
Occurrence, risk factors, and outcomes of bone cement implantation syndrome after hemi and total hip arthroplasty in cancer patients
Authors: Schwarzkopf Eugenia , Sachdev Ridhi , Flynn Jessica , Boddapati Venkat , Padilla Roger E. , Prince Daniel E. 
Published: August 2019

AbstractBackground and ObjectivesPatients undergoing cement fixation for hip arthroplasty are at increased risk of developing bone cement implantation syndrome (BCIS). We sought to determine: what is the occurrence of BCIS in patients with cancer after hip arthroplasty? What are the risk factors in patients with cancer for the development of this syndrome? What is the outcome for patients with cancer having BCIS?MethodsWe identified 374 patients with cancer who underwent cemented hip arthroplasty between 2010 and 2014. Patient characteristics, operative variables, and outcomes were collected.ResultsBCIS occurred in 279 (75%) patients. A total of 353 (94%) patients had bone metastases and 179 (48%) patients had lung metastases at the time of surgery. Age greater than 60 (hazard ratio [HR] 2.09, P = .02) and the presence of lung metastases (HR 1.77, P = .019) were associated with increased risk of BCIS. Increased perioperative use of vasopressors (HR 1.72, P = .023) and increased hospital stay beyond 10 days (HR 2.67, P = .003) was associated with BCIS.ConclusionsBCIS is a frequent clinical event in patients with cancer undergoing femoral cemented arthroplasty with increased risk for patients over age 60 and those with compromised lung function due to lung metastases and lung cancer. Patients who develop BCIS are more likely to require longer postoperative hospitalization. Careful preoperative assessment and intraoperative communication are crucial steps to reduce the consequences of BCIS.
IRX5 promotes colorectal cancer metastasis by negatively regulating the core components of the RHOA pathway
Authors: Zhu Qiangqiang , Wu Yiqi , Yang Mengli , Wang Zhen , Zhang Hailing , Jiang Xinying , Chen Meng , Jin Tianyu , Wang Ting 
Published: August 2019

AbstractColorectal cancer (CRC) is one of the most common malignant tumors worldwide. As tumor metastasis is the leading cause of death in patients with CRC, it is important to elucidate the molecular mechanisms that drive CRC metastasis. Studies have shown a close relationship between Iroquois homeobox (IRX) family genes and multiple cancers, while the mechanism by which IRX5 promotes CRC metastasis is unclear. Therefore, we focused on the involvement of IRX5 in CRC metastasis. In this study, analyses of clinical data indicated that the expression of IRX5 was coincided with metastatic colorectal tumors tissues and was negatively correlated with the overall survival of patients with CRC. Functional analysis showed that IRX5 promoted the migration and invasion of CRC cells, accompanied by a large number of cellular protrusions. IRX5‐overexpressing cells were more likely to form metastatic tumors in nude mice. Further analysis demonstrated that the core components of the RHOA/ROCK1/LIMK1 pathway were significantly inhibited in IRX5‐overexpressing cells. Overexpression of LIMK1 effectively reversed the enhanced cellular motility caused by IRX5 overexpression. Moreover, we found that high levels of IRX5 in intestinal tissues were correlated with the inflammatory response. IRX5 was significantly increased in azoxymethane/dextran sodium sulfate intestinal tissue of mice and IRX5‐overexpressing may also enhance chemokines CXCL1 and CXCL8. In summary, our findings suggested that IRX5 promoted CRC metastasis by inhibiting the RHOA‐ROCK1‐LIMK1 axis, which correlates with a poor prognosis.
Probing Binding Landscapes and Molecular Recognition Mechanisms of Atypical Antipsychotic Drugs towards the Selective Targeting of D2 Dopamine Receptor
Authors: Appiah‐Kubi Patrick , Olotu Fisayo Andrew , Soliman Mahmoud E. S. 
Published: August 2019

AbstractDopamine receptors constitute a unique class of G‐protein coupled receptors that mediate the activities of dopamine, a neurotransmitter implicated in diverse neurological diseases when dysregulated. Over the years, antipsychotic drugs have been primarily directed towards D2 dopamine receptor (DRD2) while associable adverse effects have been centred on non‐selective targeting. The recent crystal structure of DRD2 in complex with atypical antipsychotic could further aid the structure‐based design of highly DRD2‐selective antipsychotics. Therefore, in this study, we comprehensively investigate the molecular recognition and differential binding landscapes of class‐I and II DRD2 atypical antipsychotics, using membrane‐bilayer molecular dynamics simulation and binding free energy techniques. Findings revealed that selected class‐I antipsychotics exhibited binding dynamics and poses dissimilar to the class‐II types with different interactive mechanisms at the binding cavity of DRD2. More interestingly, the class‐II drugs established a highly coordinated binding at the DRD2 active site with a pertinent and recurrent involvement of Asp114 via strong hydrogen interactions. Furthermore, while these compounds exert distinct effects on DRD2 structure, findings revealed that the class‐II types favourably engaged the deep hydrophobic pocket of DRD2 compared to the class‐I drugs. We speculate that these findings will be fundamental to the discovery of highly selective DRD2 antipsychotics.
Spontaneous voiding is surprisingly recoverable via outlet procedure in men with underactive bladder and documented detrusor underactivity on urodynamics
Authors: Dobberfuhl Amy D. , Chen Annie , Alkaram Ahmed F. , De Elise J.B. 
Published: August 2019

AbstractAimsTo identify clinical and urodynamic factors leading to spontaneous voiding in men with detrusor underactivity (DU) and suspected bladder outlet obstruction who underwent an outlet de‐obstruction procedure.MethodsWe identified 614 men who underwent an outlet procedure at our institution from 2005 to 2014. Men were stratified by bladder contractility index (BCI). The primary outcome was spontaneous voiding after surgery. Data were analyzed in Statistical analysis system software.ResultsOf the 131 men who underwent preoperative urodynamics, 122 (mean age 68 years) had tracings available for review. DU (BCI < 100) was identified in 54% (66 of 122), of whom only 68% (45 of 66) voided spontaneously before surgery, compared with 82% (46 of 56) of men with BCI ≥ 100. At a mean follow‐up of 6.4 months postoperatively, 79% (52 of 66) of men with DU were able to void spontaneously, compared with 96% (54 of 56) of men with BCI ≥ 100. In men with a BCI < 100 unable to void before surgery, 57% (12 of 21) recovered spontaneous voiding after surgery. On logistic regression for the outcome postoperative spontaneous voiding, significant preoperative characteristics, and urodynamic factors included preoperative spontaneous voiding (odds ratio [OR] = 9.460; 95% confidence interval [CI] = 2.955‐30.289), increased maximum flow rate (Qmax; OR = 1.184; 95% CI = 1.014‐1.382), increased detrusor pressure at maximum flow (Pdet@Qmax; OR = 1.032; 95% CI = 1.012‐1.052), DU with BCI < 100 (OR = 0.138; 95% CI = 0.030‐0.635), and obstruction with bladder outlet obstruction index > 40 (OR = 5.595; 95% CI = 1.685‐18.575).ConclusionOutlet de‐obstruction improves spontaneous voiding in men with DU and may benefit men who do not meet the urodynamic threshold for obstruction.