bluuebunny/crossref_metadata_2025 huggingface dataset:
Durable intracranial and extracranial response to nivolumab with appearance of secondary resistance in a heavily pretreated patient with head and neck cancer
Authors: Cabezas‐Camarero Santiago , García‐Barberán Vanesa , Sáiz‐Pardo Sanz Melchor , Cabrera‐Martín María Nieves , Gimeno‐Hernández Jesús , Pérez‐Segura Pedro
Published: January 2019

Background

Recently, nivolumab was approved in the second‐line setting of squamous cell cancer of the head and neck (SCCHN). The benefits of PD‐(L)1 inhibitors in PD‐L1(−) tumors are unclear, and no reports exist on the activity of these agents in brain metastases from SCCHN. Little is known regarding the mechanisms underlying acquired resistance to PD‐(L)1 inhibition.

Methods

A patient with PD‐L1(−) metastatic SCCHN progressing to cetuximab‐based chemotherapy received third‐line nivolumab. T cell infiltration and mRNA expression of immune‐related genes were compared in prenivolumab and postnivolumab biopsies from a progressing tumor lesion.

Results

An exceptional local and systemic response was achieved, including complete devitalization of brain metastases that lasted for more than a year. Increased T cell infiltration and upregulation of genes related to T cell exhaustion and resistance to PD‐1 inhibition were found.

Conclusion

Durable responses to PD‐(L)1 inhibitors may be observed in biomarker‐negative SCCHN. Mechanisms of resistance should be studied.
Not CD68 but stabilin‐1 expression is associated with the risk of recurrence in patients with oral cavity squamous cell carcinoma
Authors: Kwon Minsu , Yeo Seong Chul , Lee Jong Sil , Park Jung Je
Published: January 2019

Background

This study's aim was to identify CD68 and stabilin‐1 expressions and their prognostic implications in patients with oral cavity cancer (OCC).

Methods

Stabilin‐1 and CD68 immunochemical staining was conducted in samples from patients with OCC who underwent curative surgery in our institute. We retrospectively analyzed patients' clinical information. We investigated the relationship between CD68 and stabilin‐1 expression levels and their effect on prognostic factors and survival.

Results

Fifty‐four patients' data were analyzed. CD68 and stabilin‐1 expressions were positively correlated (P = .008). CD68 and stabilin‐1 expressions were not correlated with other prognostic factors (eg, T classification or lymph node metastasis). Stabilin‐1 expression and tumor recurrence risk were positively correlated (P = .015). CD68 expression was neither associated with recurrence‐free nor OCC‐specific survival.

Conclusion

CD68 and stabilin‐1 expressions in OCC were positively correlated. Stabilin‐1 expression was significantly associated with OCC recurrence risk, but the prognostic value of CD68 was not confirmed.
Louis Pasteur, Chemist: An Account of His Studies of Cinchona Alkaloids
Authors: Gal Joseph
Published: January 2019

Pasteur carried out pioneering work on cinchona alkaloids and their derivatives and his studies led to important discoveries. He examined crystals of cinchona alkaloids for his correlation of crystal hemihedrism with molecular chirality, studies that led Pasteur to the discovery of physicochemical differences between diastereoisomeric salts of tartaric acids with optically active cinchona bases, an important insight into fundamentals of molecular chirality. These physicochemical differences also led to Pasteur’s invention of the vital method of racemate resolution through diastereoisomeric derivatives. Pasteur clarified the confusion around the cinchona alkaloids by elucidating their identities and relations. He discovered the conversion of the major cinchona alkaloids to quinicine and cinchonicine, a finding subsequently of considerable importance in studies of the structure and synthesis of the major cinchona alkaloids. The reaction producing quinicine and cinchonicine led Pasteur to the discovery of the racemization of tartaric acid and the finding of meso‐tartaric acid, fundamental breakthroughs in the development of stereochemistry.
Subsidiary staffing, cultural friction, and subsidiary performance: Evidence from Korean subsidiaries in 63 countries
Authors: Singh Deeksha , Pattnaik Chinmay , Lee Jeoung Yul , Gaur Ajai S.
Published: January 2019

Drawing from the notion of cultural friction and based on the agency theory rationalization of multinational enterprise (MNE) headquarter–subsidiary relationship, we examine the impact of cultural friction in foreign subsidiaries on subsidiary performance. We argue that cultural friction, arising due to a high presence of parent country nationals (PCNs) in culturally distant locations, has a detrimental effect on subsidiary performance. This effect is the strongest when the cultural friction is at the top management team (TMT) level and the weakest when friction is at the regular employee level. However, this relationship is contingent on factors that work as drags or lubricants for cultural friction between PCNs and host country nationals (HCNs). We identify governance mode and language differences between home and host countries as drag parameters and host country experience and subsidiary interdependence as lubricants that condition the effect of cultural friction on subsidiary performance. Empirical findings based on a longitudinal sample of 7,495 foreign subsidiary observations of 467 Korean MNEs in 63 countries during 1990–2014 provide robust support for our theoretical predictions.
Ambient air pollution and incident bladder cancer risk: Updated analysis of the Spanish Bladder Cancer Study
Authors: Turner Michelle C. , Gracia‐Lavedan Esther , Cirac Marta , Castaño‐Vinyals Gemma , Malats Núria , Tardon Adonina , Garcia‐Closas Reina , Serra Consol , Carrato Alfredo , Jones Rena R. , Rothman Nathaniel , Silverman Debra T. , Kogevinas Manolis
Published: January 2019

Although outdoor air pollution and particulate matter in outdoor air have been consistently linked with increased lung cancer risk, the evidence for associations at other cancer sites is limited. Bladder cancer shares several risk factors with lung cancer and some positive associations of ambient air pollution and bladder cancer risk have been observed. This study examined associations of ambient air pollution and bladder cancer risk in the large‐scale Spanish Bladder Cancer Study. Estimates of ambient fine particulate matter (PM2.5) and nitrogen dioxide (NO2) concentrations were assigned to the geocoded participant residence of 938 incident bladder cancer cases and 973 hospital controls based on European multicity land‐use regression models. Adjusted odds ratios (ORs) and 95% confidence intervals (CI) for associations of ambient air pollution and bladder cancer risk were estimated using unconditional logistic regression models. Overall, there was no clear association between either ambient PM2.5 (OR per 5.9 μg/m3 = 1.06, 95% CI 0.71–1.60) or NO2 (OR per 14.2 μg/m3 = 0.97, 95% CI 0.84–1.13) concentrations and incident bladder cancer risk. There was no clear evidence for effect modification according to age group, sex, region, education, cigarette smoking status, or pack‐years. Results were also similar among more residentially stable participants and in two‐pollutant models. Overall, there was no clear evidence for associations of ambient PM2.5 and NO2 concentrations and incident bladder cancer risk. Further research in other large‐scale population studies is needed with detailed information on measured or modeled estimates of ambient air pollution concentrations and individual level risk factors.
β6‐integrin serves as a novel serum tumor marker for colorectal carcinoma
Authors: Bengs Susan , Becker Eugenia , Busenhart Philipp , Spalinger Marianne R. , Raselli Tina , Kasper Stephanie , Lang Silvia , Atrott Kirstin , Mamie Celine , Vavricka Stephan R. , von Boehmer Lotta , Knuth Alexander , Tuomisto Anne , Mäkinen Markus J. , Hruz Petr , Turina Matthias , Rickenbacher Andreas , Petrowsky Henrik , Weber Achim , Frei Pascal , Halama Marcel , Jenkins Gisli , Sheppard Dean , Croner Roland S. , Christoph Jan , Britzen‐Laurent Nathalie , Naschberger Elisabeth , Schellerer Vera , Stürzl Michael , Fried Michael , Rogler Gerhard , Scharl Michael
Published: January 2019

Colorectal cancer (CRC) is one of the leading causes of cancer‐related deaths worldwide and the need for novel biomarkers and therapeutic strategies to improve diagnosis and surveillance is obvious. This study aims to identify β6‐integrin (ITGB6) as a novel serum tumor marker for diagnosis, prognosis, and surveillance of CRC. ITGB6 serum levels were validated in retro‐ and prospective CRC patient cohorts. ITGB6 serum levels were analyzed by ELISA. Using an initial cohort of 60 CRC patients, we found that ITGB6 is present in the serum of CRC, but not in non‐CRC control patients. A cut‐off of ≥2 ng/mL ITGB6 reveals 100% specificity for the presence of metastatic CRC. In an enlarged study cohort of 269 CRC patients, ITGB6 predicted the onset of metastatic disease and was associated with poor prognosis. Those data were confirmed in an independent, prospective cohort consisting of 40 CRC patients. To investigate whether ITGB6 can also be used for tumor surveillance, serum ITGB6‐levels were assessed in 26 CRC patients, pre‐ and post‐surgery, as well as during follow‐up visits. After complete tumor resection, ITGB6 serum levels declined completely. During follow‐up, a new rise in ITGB6 serum levels indicated tumor recurrence or the onset of new metastasis as confirmed by CT scan. ITGB6 was more accurate for prognosis of advanced CRC and for tumor surveillance as the established marker carcinoembryonic antigen (CEA). Our findings identify ITGB6 as a novel serum marker for diagnosis, prognosis, and surveillance of advanced CRC. This might essentially contribute to an optimized patient care.
LIPG‐promoted lipid storage mediates adaptation to oxidative stress in breast cancer
Authors: Cadenas Cristina , Vosbeck Sonja , Edlund Karolina , Grgas Katharina , Madjar Katrin , Hellwig Birte , Adawy Alshaimaa , Glotzbach Annika , Stewart Joanna D. , Lesjak Michaela S. , Franckenstein Dennis , Claus Maren , Hayen Heiko , Schriewer Alexander , Gianmoena Kathrin , Thaler Sonja , Schmidt Marcus , Micke Patrick , Pontén Fredrik , Mardinoglu Adil , Zhang Cheng , Käfferlein Heiko U. , Watzl Carsten , Frank Saša , Rahnenführer Jörg , Marchan Rosemarie , Hengstler Jan G.
Published: January 2019

Endothelial lipase (LIPG) is a cell surface associated lipase that displays phospholipase A1 activity towards phosphatidylcholine present in high‐density lipoproteins (HDL). LIPG was recently reported to be expressed in breast cancer and to support proliferation, tumourigenicity and metastasis. Here we show that severe oxidative stress leading to AMPK activation triggers LIPG upregulation, resulting in intracellular lipid droplet accumulation in breast cancer cells, which supports survival. Neutralizing oxidative stress abrogated LIPG upregulation and the concomitant lipid storage. In human breast cancer, high LIPG expression was observed in a limited subset of tumours and was significantly associated with shorter metastasis‐free survival in node‐negative, untreated patients. Moreover, expression of PLIN2 and TXNRD1 in these tumours indicated a link to lipid storage and oxidative stress. Altogether, our findings reveal a previously unrecognized role for LIPG in enabling oxidative stress‐induced lipid droplet accumulation in tumour cells that protects against oxidative stress, and thus supports tumour progression.
Photobiomodulation preconditioning prevents cognitive impairment in a neonatal rat model of hypoxia‐ischemia
Authors: Yang Luodan , Dong Yan , Wu Chongyun , Li Yong , Guo Yichen , Yang Baocheng , Zong Xuemei , Hamblin Michael R. , Liu Timon C.‐Y. , Zhang Quanguang
Published: January 2019

Neonatal hypoxia‐ischemia (HI) injury caused by oxygen deprivation is the most common cause of mortality and severe neurologic deficits in neonates. The present work evaluated the preventative effect of photobiomodulation (PBM) preconditioning, and its underlying mechanism of action on brain damage in an HI model in neonatal rats. According to the optimal time response of ATP levels in brain samples removed from normal rats, a PBM preconditioning (PBM‐P) regimen (808 nm CW laser, 1 cm2 spot, 100 mW/cm2, 12 J/cm2) was delivered to the scalp 6 hours before HI. PBM‐P significantly attenuated cognitive impairment, volume shrinkage in the brain, neuron loss, dendritic and synaptic injury after HI. Further mechanistic investigation found that PBM‐P could restore HI‐induced mitochondrial dynamics and inhibit mitochondrial fragmentation, followed by a robust suppression of cytochrome c release, and prevention of neuronal apoptosis by inhibition of caspase activation. Our work suggests that PBM‐P can attenuate HI‐induced brain injury by maintaining mitochondrial dynamics and inhibiting the mitochondrial apoptotic pathway.
Endoscopic optical coherence tomography angiography using a forward imaging piezo scanner probe
Authors: Wurster Lara M. , Shah Ronak N. , Placzek Fabian , Kretschmer Simon , Niederleithner Michael , Ginner Laurin , Ensher Jason , Minneman Michael P. , Hoover Erich E. , Zappe Hans , Drexler Wolfgang , Leitgeb Rainer A. , Ataman Çağlar
Published: January 2019

A forward imaging endoscope for optical coherence tomography angiography (OCTA) featuring a piezoelectric fiber scanner is presented. Imaging is performed with an optical coherence tomography (OCT) system incorporating an akinetic light source with a center wavelength of 1300 nm, bandwidth of 90 nm and A‐line rate of 173 kHz. The endoscope operates in contact mode to avoid motion artifacts, in particular, beneficial for OCTA measurements, and achieves a transversal resolution of 12 μm in air at a rigid probe size of 4 mm in diameter and 11.3 mm in length. A spiral scan pattern is generated at a scanning frequency of 360 Hz to sample a maximum field of view of 1.3 mm. OCT images of a human finger as well as visualization of microvasculature of the human palm are presented both in two and three dimensions. The combination of morphological tissue contrast with qualitative dynamic blood flow information within this endoscopic imaging approach potentially enables improved early diagnostic capabilities of internal organs for diseases such as bladder cancer.
Platelet‐derived growth factor‐D expression mediates the effect of differentiated degree on prognosis in epithelial ovarian cancer
Authors: Yang Chunyan , Zhang Mengjun , Cai Yuqing , Rong Zhiwei , Wang Ce , Xu Zhenyi , Xu Huan , Song Wei , Hou Yan , Lou Ge
Published: January 2019

Platelet‐derived growth factor‐D (PDGF‐D) can enhance invasion and metastasis in several human malignancies. Although several studies have been performed to investigate the association between clinicopathological characteristics and prognosis in epithelial ovarian cancer (EOC), the mediation effect of PDGF‐D on above‐mentioned association have been seldom assessed. In this study, we detected the PDGF‐D expression from the tissues of patients with EOC and further collected clinicopathological characteristics and prognostic information to identify whether PDGF‐D mediated the effect of differentiated degree on prognosis in patients with EOC. A total of 190 paraffin‐embedded tissue samples from patients with EOC between July 2005 and December 2010 were collected. We performed a Kaplan‐Meier analysis for the association between differentiated degree and prognosis followed by a causal mediation analysis. The analysis results indicated that differentiated degree was associated with prognosis and PDGF‐D mediated the effect of differentiated degree on prognosis in patients with EOC, which might be a potential target for ovarian cancer treatment.
MicroRNA‐29b regulates hypertrophy of murine mesenchymal stem cells induced toward chondrogenesis
Authors: Zhao Chunrong , Miao Ying , Cao Zhen , Shi Jian , Li Jianmei , Kang Fei , Dou Ce , Xie Zhao , Xiang Qiang , Dong Shiwu
Published: January 2019

Objective

Chondrocyte hypertrophy, a terminal stage of chondrocyte differentiation, is essential to the endochondral bone formation and is one of the major pathological factors in osteoarthritis. This study investigated the role of microRNA‐29b (miR‐29b), which is involved in chondrogenesis, in the regulation of hypertrophy in chondrocytes.

Methods

miR‐29b expression was assessed during murine mesenchymal stem cells (mMSCs) chondrogenesis. To detect whether miR‐29b affects chondrocyte hypertrophy, the mMSCs induced toward chondrogenesis were transfected with miR‐29b or its antisense inhibitor (antagomiR‐29b). Finally, the differential effects of antagomiR‐29b on chondrocytes at different differentiation stages were evaluated by loss‐of‐function experiments.

Results

miR‐29b expression was low‐level during the early chondrogenic differentiation, however, it was changed to high level during hypertrophy. Subsequently, the gain‐of‐function and loss‐of‐function experiments had confirmed that miR‐29b promoted hypertrophy in mMSC‐derived chondrocytes. In addition, we confirmed that on day 7, when cells were treated with antagomiR‐29b, was the optimal intervention time for preventing hypertrophic phenotype of mMSCs in vitro.

Conclusion

miR‐29b regulated chondrogenesis homeostasis and enhance hypertrophic phenotype. These data suggest that miR‐29b is a key regulator of the chondrocyte phenotype derived from mMSCs and it might be a potential target for articular cartilage repair.
Silence of  lncRNA UCA1 rescues drug resistance of cisplatin to non–small‐cell lung cancer cells
Authors: Liu Xiaojing , Huang Zhisheng , Qian Wei , Zhang Qing , Sun Jian
Published: January 2019

The aim of this study was to investigate the effect of long noncoding RNA (lncRNA) urogenital carcinoma antigen 1 (UCA1) on drug resistance in A549/DDP cell and explore its underlying mechanism. The inhibition rate and IC
50 of DDP were detected in A549 and A549/DDP cells by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5 diphenyl tetrazolium bromide assay. The expression of lncRNA UCA1 was measured in A549 and A549/DDP cells by quantitative real‐time polymerase chain reaction. The expressions of N‐cadherin, E‐cadherin, vimentin, and Snail were detected in A549 and A549/DDP cells by Western blot analysis. Results showed that the IC
50 of DDP was 16.20 ± 2.27 μmol/L and 69.72 ± 4.83 μmol/L in A549 and A549/ DDP cells, respectively. Compared with the A549 group, the expressions of N‐cadherin, vimentin, and Snail was significantly upregulated in A549/DDP group, but E‐cadherin was significantly downregulated. Compared with the shCon group, the abundance of N‐cadherin, vimentin, and Snail was significantly downregulated in short hairpin RNA UCA1 (shUCA1) group, while E‐cadherin was significantly upregulated. Cell migration and invasion were significantly suppressed and IC
50 was reversed to 16.20 ± 2.27 μmol/L in the shUCA1 group. Silencing lncRNA UCA1 inhibited the migration and invasion of A549/DDP cells and reversed the resistance of A549/DDP cells to DDP. The mechanism might be related to downregulation of epithelial‐mesenchymal transition, which will provide a new direction for the treatment of non–small‐cell lung cancer with cisplatin.
Menadione‐induced apoptosis in U937 cells involves Bid cleavage and stefin B degradation
Authors: Božič Janja , Bidovec Katja , Vizovišek Matej , Dolenc Iztok , Stoka Veronika
Published: January 2019

Earlier studies showed that the oxidant menadione (MD) induces apoptosis in certain cells and also has anticancer effects. Most of these studies emphasized the role of the mitochondria in this process. However, the engagement of other organelles is less known. Particularly, the role of lysosomes and their proteolytic system, which participates in apoptotic cell death, is still unclear. The aim of this study was to investigate the role of lysosomal cathepsins on molecular signaling in MD‐induced apoptosis in U937 cells. MD treatment induced translocation of cysteine cathepsins B, C, and S, and aspartic cathepsin D. Once in the cytosol, some cathepsins cleaved the proapoptotic molecule, Bid, in a process that was completely prevented by E64d, a general inhibitor of cysteine cathepsins, and partially prevented by the pancaspase inhibitor, z‐VAD‐fmk. Upon loss of the mitochondrial membrane potential, apoptosome activation led to caspase‐9 processing, activation of caspase‐3‐like caspases, and poly (ADP‐ribose) polymerase cleavage. Notably, the endogenous protein inhibitor, stefin B, was degraded by cathepsin D and caspases. This process was prevented by z‐VAD‐fmk, and partially by pepstatin A‐penetratin. These findings suggest that the cleaved Bid protein acts as an amplifier of apoptotic signaling through mitochondria, thus enhancing the activity of cysteine cathepsins following stefin B degradation.
Clinical case report of patients with osteosarcoma and anticancer benefit of calycosin against human osteosarcoma cells
Authors: Qiu Rubiao , Ma Gang , Li Xueyu , Shi Qunfeng , Li Xinning , Zhou Xiong , Tang Yuanyuan , Xie Zhaodi , Liao Shijie , Qin Yiwu , Wang Ruyue , Ye Yu , Luo Jiefeng , Zhang Jianfeng
Published: January 2019

Osteosarcoma (OS) is a malignant neoplasia in bone, characterized with main occurrence in teenagers. Calycosin (CC), a bioactive compound, is found to play potent pharmacological effects against cancer. Our previous study indicates CC‐exerted benefits for anti‐OS effect. However, further molecular mechanism behind this action needs to be investigated. In this study, human OS samples and clinical data were collected and used for further test and analysis. In addition, human osteosarcoma cell line (143B) and tumor‐xenograft nude mice were used to evaluate antineoplastic activities of CC through a series of biochemical methods and immunoassays, respectively. Compared with non‐OS controls, human OS samples showed increased levels of neoplastic microRNA‐223 (miR‐223), and elevated expressions of NF‐κBp65, IκBα proteins in tumor cells. In cell culture study, CC‐treated 143B cells showed reduced cell growth, increased lactic dehydrogenase (LD) content, and downregulated cellular miR‐223 level. Immunolabeled cells of proliferating cell nuclear antigen, B‐cell lymphoma 2 (Bcl‐2), poly(ADP‐ribose) polymerase (PARP) in CC treatments were decreased dose‐dependently, while caspase‐3 positive cells were elevated. Further, protein expressions of NF‐κBp65, IκBα in CC‐treated cells were downregulated. In addition, tumor‐xenograft nude mice followed by CC treatments exhibited reductions of tumor mass, miR‐223 levels, and Bcl‐2, PARP‐positive cells, as well as downregulations of NF‐κBp65, IκBα protein expressions in OS samples. Taken together, these experimental findings reveal that CC exhibits potential pharmacological activities against OS through inducing apoptosis and inhibiting miR‐223‐IκBα signaling pathway in neoplastic cells.
AZD8835 inhibits osteoclastogenesis and periodontitis‐induced alveolar bone loss in rats
Authors: Wang Yexin , Chen Xuzhuo , Chen Xinwei , Zhou Zhihang , Xu Weifeng , Xu Feng , Zhang Shanyong
Published: January 2019

Chronic periodontitis (CP) is one of the most common oral diseases, which is characterized by the loss of connective tissue and alveolar bone in adults. AZD8835, a novel dual phosphoinositide‐3‐kinase (PI3K) inhibitor, is currently in phase 1 clinical evaluation to treat breast cancer. However, whether AZD8835 has any effect on teeth and alveolar bone health remains unclear. In the current study, we aimed to investigate the potential effect of AZD8835 in treating CP in vitro and in vivo. We found that AZD8835 could inhibit osteoclast differentiation, bone resorption, and downregulate the expression of osteoclast marker genes, such as tartrate‐resistant acid phosphatase (Trap), cathepsin K (Ctsk), V‐ATPase d2 (Atp6v0d2), and calcitonin receptor (Ctr). In addition, AZD8835 suppressed osteoclastogenesis by inhibiting receptor activator of nuclear factor kappa B ligand (RANKL)‐induced PI3K/protein kinase B (AKT), extracellular signal‐regulated kinase, and nuclear factor‐κB signaling in BMMs. In vivo, AZD8835 greatly ameliorated alveolar bone (ABL) loss in rats with CP. Meanwhile, histological examination showed fewer osteoclasts in the treatment group. In conclusion, these results indicated that AZD8835 is a promising agent to reduce ABL in CP.
Efficacy and acceptability of neoadjuvant endocrine therapy in patients with hormone receptor‐positive breast cancer: A network meta‐analysis
Authors: Zhang Tingting , Feng Fubin , Yao Yan , Qi Lingyu , Tian Jinhui , Zhou Chao , Dong Shengjie , Wang Xue , Sun Changgang
Published: January 2019

Background

The optimal sequence of endocrine therapy in a neoadjuvant setting for hormone receptor‐positive (HR+) breast cancer is unclear. Our study evaluated the efficacy and acceptability of neoadjuvant endocrine therapy for HR+ breast cancer.

Methods

We identified studies based on titles and abstracts that were published before 22 June 2018 in the following databases: PubMed, EMBASE, and the Cochrane Library. Eligible studies were randomised controlled trials with at least one arm that evaluated the effectiveness of one or a combination of anastrozole, letrozole, palbociclib, tamoxifen, fulvestrant, abemaciclib, everolimus, gefitinib, ribociclib, taselisib, and exemestane. We pooled effect sizes using the odds ratio (OR) and corresponding 95% credibility interval (95% CrI). The primary outcomes were response rate and treatment completion.

Results

Our network meta‐analysis included 3,306 participants and 16 eligible studies, which assessed 15 treatments. In terms of response rates, compared with letrozole combined therapy, tamoxifen was associated with a significant reduction in response rate (OR, 0.34; 95% CrI, 0.13–0.85; OR, 0.32; 95% CrI, 0.13–0.80; OR, 0.26; 95% CrI, 0.09–0.83; and OR, 0.30; 95% CrI, 0.09–0.96; for letrozole plus everolimus, letrozole plus taselisib, letrozole plus zoledronic acid, and letrozole plus lapatinib, respectively). Based on the surface under the cumulative ranking curves ranking, letrozole plus zoledronic acid was associated with the highest rate of response (87.6%), followed by letrozole plus lapatinib (85.2%), and letrozole plus taselisib (79.3%).

Conclusions

Ultimately, our study established that letrozole plus zoledronic acid may be an optimal treatment based on its current rank in a neoadjuvant setting for HR+ breast cancer.
Impact of hyperoxia on cardiac pathophysiology
Authors: Rodgers Jennifer L. , Iyer Drishya , Rodgers Lydia E. , Vanthenapalli Sahit , Panguluri Siva K.
Published: January 2019

Mechanical ventilation with high oxygen therapy (hyperoxia) is widely implemented in critical care and ICU settings. Although supplemental oxygen is beneficial to treat hypoxia, its use is also associated with poor outcomes and high mortality in patients. Lung injury due to hyperoxia exposure has been well‐documented in patients, including in adults and neonates. Thus, lung injury due to hyperoxia has been extensively researched in both preclinical and clinical studies. However, hyperoxia has also been shown to be associated with hemodynamic changes in patients in ICU, including reductions in heart rate, stroke volume, and cardiac output. In addition, certain experimental studies report that hyperoxia exposure in neonates results in cardiac dysfunction in later adult life. Despite this, until recently, the impact of hyperoxia within the heart has not been well studied, or reported, specifically in adult experimental models. To close this significant gap, our lab has sought to clarify hyperoxia‐induced cardiac pathophysiology in adult murine models. This review discusses the current findings regarding the cardiovascular impact of hyperoxia exposure.
Scalable Synthesis of N‐Acetylated α‐Amino Acid‐Derived Oxazoline Ligands
Authors: Kovalenko Vitaly , Vasiutovich Kiryl
Published: January 2019

A scalable cost‐effective synthesis of promising α‐amino acid‐derived oxazoline ligands has been developed. The advantage of the reported procedures is the use of crystallization for the purification of key intermediates and final products. The ligands obtained have recently demonstrated remarkable enantioselectivity in Pd (II) catalyzed C─H activation reactions. Hence, more rational synthetic route presented here will contribute to this rapidly growing field of chemistry.
Constrained 1‐Phenylethyl Amine Analogues as Chiral Auxiliaries in Stereoselective trans‐β‐Lactam Formation via Staudinger Cycloaddition
Authors: Kurteva Vanya , Alexandrova Maria
Published: January 2019

The efficiency of enantiomeric 1‐aminoindane and 1,2,3,4‐tetrahydro‐1‐naphthylamine as chiral auxiliaries in trans‐ß‐lactam formation via Staudinger cycloaddition is examined. Aromatic aldehydes possessing one, two, or three methoxyl groups are used as imine precursors, and the influence of their number and position on the reaction output is studied. A comparison with the results obtained from 1‐phenylethyl and 1‐(2‐naphthyl)ethylamine‐derived imines is performed.
Epidemiology of enteric viruses in children with gastroenteritis in Ogun State, Nigeria
Authors: Arowolo Kafayat Olushola , Ayolabi Christianah Idowu , Lapinski Bruna , Santos Jucielia Stadinicki , Raboni Sonia Mara
Published: January 2019

Acute gastroenteritis (AGE) remains a global public health concern and Nigeria is one of the two countries accounting for 42% of global under‐5 deaths attributable to gastroenteritis. This study aimed to determine the prevalence, seasonality, and risk factors of enteric viruses (EVs) in children with AGE in Ogun State, Nigeria. Stool samples collected from children under‐5 from three different hospitals between February 2015 and April 2017 were analyzed using molecular methods for the presence of four EVs (group A rotavirus [RVA], norovirus [NoV], human astrovirus [HAstV], and human adenovirus [HAdV]). Among the 175 samples analyzed, 63 (36%) were positive for at least one EV. The most prevalent was HAstV (19.4%), followed by RVA (16.6%), NoV (5.1%), and HAdV (5.1%). Mixed infections were found in 17 cases. No significant association was observed with age, sex, and risk factors. Though not significant, EV prevalence was higher in the dry season. Positive cases (asides HAdV) had no correlation with temperature and/or humidity. This study provides information on the prevalence and seasonal fluctuations of EVs, which will be of value in the effective management of patients and control strategies for viral gastroenteritis in the country.
An efficient multi‐destinations trip planning protocol for intelligent transport system
Authors: Siam Hisham , Bani Younes Maram
Published: January 2019

Targeting several destinations on the same trip is commonly seen over the downtown areas. Several drivers leave their home or work everyday targeting multiple end‐destinations for shopping or entertaining purposes. The sequence of visiting destinations can be selected randomly by the drivers, especially if they are less familiar with the area of interest or with multi‐destinations trips. However, expert drivers that travel more frequently towards several destinations should be more cautious planning their trips. They consider the relative locations of these end‐destinations and use their historical knowledge regarding the traffic over the connected road segments there. This paper proposes an efficient multi‐destinations trip planning protocol (MDPP) that recommends drivers with the best sequence of destinations to visit. The proposed protocol considers the location of each destination and the relative distance between all located destinations. It also considers the traffic distribution over the investigated areas of interest to recommend drivers to avoid highly congested road segments or road segments that suffer traffic issue such as accident or emergency existence. From the experimental results, we can see that the MDPP protocol has selected the best path towards the targeted destinations compared with other common selected sequences. It has decreased the travel time, fuel consumption, and the gas emissions for different investigated scenarios.
Molecular signatures of chronic periodontitis in gingiva: A genomic and proteomic analysis
Authors: Guzeldemir‐Akcakanat Esra , Alkan Begum , Sunnetci‐Akkoyunlu Deniz , Gurel Busra , Balta V. Merve , Kan Bahadir , Akgun Emel , Yilmaz Elif Busra , Baykal Ahmet Tarik , Cine Naci , Olgac Vakur , Gumuslu Esen , Savli Hakan
Published: January 2019

Background

To elucidate molecular signatures of chronic periodontitis (CP) using gingival tissue samples through omics‐based whole‐genome transcriptomic and whole protein profiling.

Methods

Gingival tissues from 18 CP and 25 controls were analyzed using gene expression microarrays to identify gene expression patterns and the proteins isolated from these samples were subjected to comparative proteomic analysis by liquid chromatography‐tandem mass spectrometry (LC‐MS/MS). The data from transcriptomics and proteomics were integrated to reveal common shared genes and proteins.

Results

The most upregulated genes in CP compared with controls were found as MZB1, BMS1P20, IGLL1/IGLL5, TNFRSF17, ALDH1A1, KIAA0125, MMP7, PRL, MGC16025, ADAM11, and the most upregulated proteins in CP compared with controls were BPI, ITGAM, CAP37, PCM1, MMP‐9, MZB1, UGTT1, PLG, RAB1B, HSP90B1. Functions of the identified genes were involved cell death/survival, DNA replication, recombination/repair, gene expression, organismal development, cell‐to‐cell signaling/interaction, cellular development, cellular growth/proliferation, cellular assembly/organization, cellular function/maintenance, cellular movement, B‐cell development, and identified proteins were involved in protein folding, response to stress, single‐organism catabolic process, regulation of peptidase activity, and negative regulation of cell death. The integration and validation analysis of the transcriptomics and proteomics data revealed two common shared genes and proteins, MZB1 and ECH1.

Conclusion

Integrative data from transcriptomics and proteomics revealed MZB1 as a potent candidate for chronic periodontitis.
Surgical treatment of posterior mediastinal neurogenic tumors
Authors: Chen Xiaofeng , Ma Qinyun , Wang Shaohua , Zhang Huijun , Huang Dayu
Published: January 2019

Background

Posterior mediastinal neurogenic tumors are among the most frequent mediastinal masses in adults. These tumors may be dumbbell shaped, extending into the spinal canal, exclusively paraspinal or apical tumors extending in the cervical region. In this report, we present our experience in the surgical resection of these tumors and discuss the surgical strategies for such tumors.

Methods

A retrospective analysis was performed of 121 patients who underwent surgery for posterior mediastinal neurogenic tumors at our department during the period 2009 to 2016. Seventy‐four tumors were excised via video‐assisted thoracic surgery (VATS). Other approaches included thoracotomy, supraclavicular incision, supraclavicular incision plus thoracotomy/VATS, and a posterior approach with laminectomy combined with thoracotomy/VATS.

Results

Tumors were resected completely in 119 cases and partially in two. The majority of the tumors were benign nerve sheath tumors. No recurrence developed during postoperative median follow‐up period of 31 months.

Conclusion

Most posterior neurogenic tumors can be resected via VATS. Thoracotomy is the appropriate surgical approach for large tumors. A supraclavicular approach is recommended for tumors extending in the cervical region, and this can be combined with VATS or thoracotomy in case of larger masses. A posterior approach could be used for patients with dumbbell tumors.
Combination of a modified quick, easy, cheap, efficient, rugged, and safe extraction method with a deep eutectic solvent based microwave‐assisted dispersive liquid–liquid microextraction: Application in extraction and preconcentration of multiclass pesticide residues in tomato samples
Authors: Farajzadeh Mir Ali , Sohrabi Hessamaddin , Mohebbi Ali , Mogaddam Mohammad Reza Afshar
Published: January 2019

In this study, a new two–step extraction procedure based on the combination of a modified quick, easy, cheap, effective, rugged, and safe extraction method with a deep eutectic solvent based microwave‐assisted dispersive liquid–liquid microextraction has been developed for the extraction of multiclass pesticides in tomato samples before their analysis by gas chromatography with flame ionization detection. In this method, initially, an aliquot of tomato is crushed and diluted with deionized water. The mixture is then passed through a filter paper and its residue and aqueous phase are separated. Afterwards, acetonitrile as an extraction/disperser solvent is passed through the filter paper containing the refuse. The analytes remained in the refuse are extracted into the acetonitrile and then the obtained extract is mixed with a deep eutectic solvent. The obtained mixture is injected into the tomato juice and placed in a microwave oven for 15 s. Consequently, a cloudy state is formed and the extractant containing the analytes are sedimented at the bottom of the tube after centrifugation. Finally, 1 μL of the sedimented phase is removed and injected into the separation system. Under the optimum conditions, limits of detection and quantification were in the ranges of 0.42–0.74 and 1.4–2.5 ng/g, respectively.
Ligand fishing of anti‐neurodegenerative components from Lonicera japonica using magnetic nanoparticles immobilised with monoamine oxidase B
Authors: Wu Gui‐Fang , Jiang Xiao‐Lan , Gong Yu‐Zhou , Hu Ya‐Dong , Bai Xiao‐Lin , Liao Xun
Published: January 2019

In this work, monoamine oxidase B was immobilised onto magnetic nanoparticles to prepare a new type of affinity solid‐phase extraction adsorbent, which was used to extract the possible anti‐neurodegenerative components from the Lonicera japonica flower extracts. Coupled with high‐performance liquid chromatography with mass spectrometry, two monoamine oxidase B ligands were fished‐out and identified as isochlorogenic acid A and isochlorogenic acid C, which were found to be inhibitors of the enzyme for the first time, with similar half maximal inhibitory concentration values of 29.05 ± 0.49 and 29.77 ± 1.03 μM, respectively. Furthermore, equilibrium‐dialysis dissociation assay of enzyme‐inhibitor complex showed that both compounds have reversible binding patterns to monoamine oxidase B, and kinetic analysis demonstrated that they were mixed‐type inhibitors for monoamine oxidase B, with Ki and Kis values of 9.55 and 37.24 μM for isochlorogenic acid A, 9.53 and 35.50 μM for isochlorogenic acid C, respectively. The results indicated that isochlorogenic acid A and isochlorogenic acid C were the major active components responsible for the anti‐degenerative activity of the flowers of L. japonica, while magnetic nanoparticles immobilised monoamine oxidase B could serve as an efficient solid‐phase extraction adsorbent to specifically extract monoamine oxidase B inhibitors from complex herbal extracts.
Comparison Between Low Mechanical Index and High Mechanical Index Contrast Modes of Contrast‐Enhanced Ultrasonography: Evaluation of Perfusion Defects of Hypervascular Hepatocellular Carcinomas During the Post–Vascular Phase
Authors: Duisyenbi Zaya , Numata Kazushi , Nihonmatsu Hiromi , Fukuda Hiroyuki , Chuma Makoto , Kondo Masaaki , Nozaki Akito , Tanaka Katsuaki , Maeda Shin
Published: January 2019

Objectives

We evaluated the detection rates for perfusion defects in hypervascular hepatocellular carcinomas comparing the low mechanical index (MI) and high MI contrast modes during the post–vascular phase (PVP) of contrast‐enhanced ultrasonography.

Methods

Seventy‐eight patients with 84 hypervascular hepatocellular carcinomas (mean diameter, 23.4 ± 11.2 mm) were selected for this retrospective study. All the patients underwent whole‐liver scanning using conventional ultrasonography before injection of a perflubutane‐based contrast agent (Sonazoid), and all the detected nodules were classified as either hypoechoic or hyperechoic nodules. Next, hypoechoic and hyperechoic nodules were evaluated using contrast‐enhanced ultrasonography, and the presence of a perfusion defect was assessed for each nodule using both the low MI (0.2–0.3) and the high MI (0.7–1.2) contrast modes during the PVP (10 minutes after injection). The data were analyzed using the McNemar test.

Results

Forty‐four nodules were classified as hypoechoic nodules, and the remaining 40 nodules were classified as hyperechoic nodules using conventional ultrasonography. The detection rate for perfusion defects determined using the high MI contrast mode was higher than that determined using the low MI contrast mode in hyperechoic nodules during the PVP (low MI, 58% [23 of 40]; high MI, 90% [36 of 40]; P < .0001). However, no significant difference was observed between the low MI and the high MI contrast modes in hypoechoic nodules (low MI, 80% [35 of 44]; high MI, 89% [39 of 44]; P = .125).

Conclusion

Compared with the low MI contrast mode, the high MI contrast mode was more sensitive for detecting perfusion defects in hypervascular hepatocellular carcinomas in patients with hyperechoic nodules during the PVP.
Hyperspectral imaging in automated digital dermoscopy screening for melanoma
Authors: Hosking Anna‐Marie , Coakley Brandon J. , Chang Dorothy , Talebi‐Liasi Faezeh , Lish Samantha , Lee Sung Won , Zong Amanda M. , Moore Ian , Browning James , Jacques Steven L. , Krueger James G. , Kelly Kristen M. , Linden Kenneth G. , Gareau Daniel S.
Published: January 2019

Objectives

Early melanoma detection decreases morbidity and mortality. Early detection classically involves dermoscopy to identify suspicious lesions for which biopsy is indicated. Biopsy and histological examination then diagnose benign nevi, atypical nevi, or cancerous growths. With current methods, a considerable number of unnecessary biopsies are performed as only 11% of all biopsied, suspicious lesions are actually melanomas. Thus, there is a need for more advanced noninvasive diagnostics to guide the decision of whether or not to biopsy. Artificial intelligence can generate screening algorithms that transform a set of imaging biomarkers into a risk score that can be used to classify a lesion as a melanoma or a nevus by comparing the score to a classification threshold. Melanoma imaging biomarkers have been shown to be spectrally dependent in Red, Green, Blue (RGB) color channels, and hyperspectral imaging may further enhance diagnostic power. The purpose of this study was to use the same melanoma imaging biomarkers previously described, but over a wider range of wavelengths to determine if, in combination with machine learning algorithms, this could result in enhanced melanoma detection.

Methods

We used the melanoma advanced imaging dermatoscope (mAID) to image pigmented lesions assessed by dermatologists as requiring a biopsy. The mAID is a 21‐wavelength imaging device in the 350–950 nm range. We then generated imaging biomarkers from these hyperspectral dermoscopy images, and, with the help of artificial intelligence algorithms, generated a melanoma Q‐score for each lesion (0 = nevus, 1 = melanoma). The Q‐score was then compared to the histopathologic diagnosis.

Results

The overall sensitivity and specificity of hyperspectral dermoscopy in detecting melanoma when evaluated in a set of lesions selected by dermatologists as requiring biopsy was 100% and 36%, respectively.

Conclusion

With widespread application, and if validated in larger clinical trials, this non‐invasive methodology could decrease unnecessary biopsies and potentially increase life‐saving early detection events. Lasers Surg. Med. 51:214–222, 2019. © 2019 The Authors.Lasers in Surgery and MedicinePublished by Wiley Periodicals, Inc.
Learning and dynamic choices under uncertainty: From weighted regret and rejoice to expected utility
Authors: Zagonari Fabio
Published: January 2019

This paper identifies the globally stable conditions under which an individual facing the same choice in many subsequent times learns to behave as prescribed by the expected‐utility model. The analysis moves from the relevant behavioural models suggested by psychology, by updating probability estimations and outcome preferences according to the learning models suggested by neuroscience, in a manner analogous to Bayesian updating. The search context is derived from experimental economics, whereas the learning framework is borrowed from theoretical economics. Analytical results show that the expected‐utility model explains real behaviours in the long run whenever bad events are more likely than good events.
Risk of Parkinson's disease dementia related to level I MDS PD‐MCI
Authors: Hoogland Jeroen , Boel Judith A. , de Bie Rob M.A. , Schmand Ben A. , Geskus Ronald B. , Dalrymple‐Alford John C. , Marras Connie , Adler Charles H. , Weintraub Daniel , Junque Carmen , Pedersen Kenn F. , Mollenhauer Brit , Goldman Jennifer G. , Tröster Alexander I. , Burn David J. , Litvan Irene , Geurtsen Gert J. ,   on behalf of the MDS Study Group “Validation of Mild Cognitive Impairment in Parkinson Disease”
Published: January 2019

Background

The International Parkinson and Movement Disorders Society criteria for mild cognitive impairment in PD need validation. The objectives of this present study were to evaluate prognostic validity of level I (abbreviated) International Parkinson and Movement Disorders Society mild cognitive impairment in PD criteria for development of PD dementia and compared them with level II (comprehensive) criteria.

Methods

We analyzed data from 8 international studies (1045 patients) from our consortium that included baseline data on demographics, motor signs, depression, detailed neuropsychological testing, and longitudinal follow‐up for conversion to Parkinson's disease dementia. Survival analysis evaluated their contribution to the hazard of Parkinson's disease dementia.

Results

Level I mild cognitive impairment in PD, increasing age, male sex, and severity of PD motor signs independently increased the hazard of Parkinson's disease dementia. Level I and level II mild cognitive impairment in PD classification had similar discriminative ability with respect to the time to Parkinson's disease dementia.

Conclusions

Level I mild cognitive impairment in PD classification independently contributes to the hazard of Parkinson's disease dementia. This finding supports the prognostic validity of the abbreviated mild cognitive impairment in PD criteria. © 2019 International Parkinson and Movement Disorder Society
Chemoinformatic Consideration of Novel Psychoactive Substances: Compilation and Preliminary Analysis of a Categorised Dataset
Authors: Firman James W. , Belfield Samuel J. , Chen George , Jackson Megan , Lam Fai Hou , Richmond Callum , Smith James , Steinmetz Fabian P. , Cronin Mark T. D.
Published: January 2019

Recent years have seen the emergence into circulation of a growing array of novel psychoactive substances (NPS). Knowledge of the pharmacological profiles and risk liability of these compounds is typically very scarce. Development of chemoinformatic tools enabling prediction of properties within uncharacterised analogues has potential be of particular use. In order to facilitate this, compilation of a chemical inventory comprising known NPS is a necessity. Sourcing a variety of published governmental and analytical reports, a dataset composed of 690 distinct acknowledged NPS, complete with defined chemical structures, has been constructed. This is supplemented by a complementary series of 155 established psychoactive drugs of abuse (EPDA). Classification was performed in accordance with their key molecular structural features, subjective effect profiles and pharmacological mechanisms of action. In excess of forty chemical groupings, spanning seven subjective effect categories and six broad mechanisms of pharmacological action, were identified. Co‐occurrence of NPS and EPDA within specific classes was common, showcasing inherent scope both for chemical read‐across and for the derivation of structural alerts.