bluuebunny/crossref_metadata_2025 huggingface dataset:
An Experiment on Building Evaluation Capacity to Address Health Inequities in China
Authors: Zhao Kun , Sridharan Sanjeev , Ingabire Marie‐Gloriose , Yu Mo , Nakaima April , Li Xue , Xiao Yue , Chen Emily
Published: June 2017

This paper describes an evaluation experiment conducted in China between 2013 and 2016 to use evaluative thinking and evaluation approaches to help build the salience of health equity as a performance measure for health systems. This project was informed by a realist evaluation approach that sought to understand the context, mechanisms, and outcomes underlying health inequities. This chapter describes a theory of change that includes descriptions of the key actors involved in the project, the mechanisms of impact, and short‐ and long‐term outcomes. Key questions that could help assess the impact of this project are also discussed. This paper contributes to the literature on building evaluation capacity for health inequities.
Evaluation at the Time of Health Systems Reform: Chinese Policymakers’ Need for a Robust System of Evaluations to Assess Progress in the Implementation of Reform Efforts
Authors: Zhao Kun , Nakaima April , Guo Wudong , Qiu Yingpeng , Sridharan Sanjeev
Published: June 2017

In 2014 the authors of this paper, evaluators from China and Canada, jointly interviewed 12 policymakers in China at the national and provincial levels. This paper describes the needs of policymakers and how they view the evaluation capacity‐building needs of the health system. The learnings from the policymaker dialogues informed the evaluation capacity‐building efforts at three pilot sites in China. This paper focuses on the evaluation capacities needed by policymakers and implementers specifically to address inequities in the health sector, unlike most publications that focus on evaluation capacities of researchers.
Models for Applying Scholarship to Practice
Authors: Wilson Maureen E. , Hirschy Amy S.
Published: June 2017

Models for applying scholarship to practice provide guidance to administrators who are informed by research to address very complex problems.
The Scholarship of Practice and Stewardship of Higher Education
Authors: Braxton John M. , Ream Todd C.
Published: June 2017

This chapter describes the enactment of three levels of a scholarship of practice for higher education. The stewardship played by each of these levels constitutes the central focus of this chapter.
The role of cold‐inducible RNA binding protein in cell stress response
Authors: Liao Yi , Tong Lingying , Tang Liling , Wu Shiyong
Published: June 2017

Cold‐inducible RNA binding protein (CIRP) was discovered after the cells were exposed to a moderate cold shock because its production was induced. Other cellular stresses such as ultraviolet light radiation and hypoxia also could increase its expression. Under stress conditions, CIRP could up regulate its own expression by self‐transcriptional activation of alternative promoters. After relocating into cytoplasm from nucleus, CIRP assists cells in adapting to novel environmental conditions via stabilizing specific mRNAs and facilitating their translation. It not only participates in anti‐apoptosis processes under mild hypothermia condition, but also protects cells from ultraviolet radiation and hypoxia induced senescence process. This article focuses on the possible mechanisms of its inducible expression, cytoprotective functions and carcinogenesis. In addition, extracellular CIRP has been shown to be a novel danger‐associated molecular patter (DAMP) member and is able to induce inflammatory response. Finally, based on the distinct roles of CIRP in intracellular and extracellular conditions, a possible model of CIRP‐mediated cell fate has been proposed.
A meta‐analysis of pelvic floor muscle training for the treatment of urinary incontinence
Authors: Nie Xiao‐Fei , Ouyang Yan‐Qiong , Wang Lan , Redding Sharon R.
Published: June 2017

Background

Symptoms associated with urinary incontinence (UI) frequently affect quality of life.

Objectives

To assess the effects of pelvic floor muscle training (PFMT) among women with UI.

Search strategy

The Cochrane Library, PubMed, and Web of Science databases were searched using relevant terms for all English‐language studies published up to August 15, 2016.

Selection criteria

Studies that evaluated the effects of PFMT on UI symptoms, PFM function, and quality of life were included.

Data collection and analysis

Data were screened and collected by two independent investigators. Pooled effect sizes and 95% confidence intervals (CIs) were calculated.

Main results

Twelve studies were included, involving 763 patients. Use of PFMT increased PFM strength when measured by digital palpation and the Muscle Strength Oxford Scale (standardized mean difference [SMD] 1.18, 95% CI 0.56–1.80). The PFM pressure was increased by PFMT when measured using a perineometer (SMD 0.40, 95% CI 0.07–0.73). Finally, PFMT improved quality of life (SMD 1.67, 95% CI 0.41–2.94).

Conclusions

Regular use of PFMT provided symptom relief and improved quality of life among women with UI.
Effect of HIV infection on outcomes after surgical repair of genital fistula
Authors: Shephard Steven N. , Lengmang Sunday J. , Anzaku Stephen A. , Mamven Oluwatobi V. , Kirschner Carolyn V.
Published: June 2017

Objective

To compare outcomes following surgical repair of genital fistula among Nigerian women with or without HIV.

Methods

A retrospective review was conducted of all genital fistula repair surgeries performed at Evangel Vesicovaginal Fistula Center in Jos, Nigeria, between January 1, 2004, and April 30, 2014. Patient characteristics, HIV status, genital fistula characteristics, and postoperative outcomes were assessed for between‐group variance. The odds ratio (OR) and 95% confidence intervals (CIs) were the primary measures used for determining the association between HIV status and surgical outcomes.

Results

Of the 3313 surgeries recorded, 201 (6.1%) were performed among patients with HIV infection. No statistically significant between‐group differences were found for patient or fistula characteristics. By contrast, failed vesicovaginal failure (VVF) closure was significantly more common among women infected with HIV than among their HIV‐negative counterparts (OR 0.629, 95% CI 0.443–0.894). No between‐group differences in failure rates were found for ureterovaginal or rectovaginal fistulas.

Conclusion

Determining HIV status before surgery could aid prediction of outcomes among Nigerian women undergoing repair of VVF. Further studies are required to examine factors that might improve outcomes for women with HIV infection.
Determining the accuracy of pregnancy‐length dating among women presenting for induced abortions in Ghana
Authors: Shellenberg Kristen M. , Antobam Samuel K. , Griffin Risa , Edelman Alison , Voetagbe Gertrude
Published: June 2017

Objective

To determine the proportion of women presenting for an induced abortion in Ghana who could use a gestational wheel to determine if they had reached at least 13 weeks or fewer than 13 weeks of pregnancy accurately.

Methods

The present cross‐sectional study was conducted at four facilities in Ghana between February 1, and July 31, 2014. Women aged at least 18 years seeking induced abortions who had not previously been informed of the length of their pregnancy by a clinician were enrolled. Women self‐assessed pregnancy duration using a gestational wheel before a clinician assessed the length via clinical assessment and bimanual exam for use as a respective reference point. The proportion of participants who used the wheel successfully was calculated.

Results

The study enrolled 780 participants, 770 of whom used the gestational wheel. Of these, 221 (28.7%) could use the wheel without verbal instructions, and 465 (60.4%) described it as easy to use. Agreement in pregnancy‐length assessments was recorded for 728 (94.5%) patients. There were 10 (1.3%) and 28 (3.6%) participants who made evaluations with “low‐risk disagreement” and “high‐risk disagreement” with the clinician assessment, respectively.

Conclusion

Almost all participants could use the gestational wheel to date their pregnancies correctly. This tool could help women perform medical abortions safely in the community, reducing morbidity and mortality from unsafe abortions.
A cross‐sectional study exploring the incidence of and indications for second‐stage cesarean delivery over three decades
Authors: Pearson Greg A. , MacKenzie Ian Z.
Published: June 2017

Objective

To observe the incidence of, indications for, and complications associated with second‐stage cesarean delivery in 10‐year intervals over 30 years.

Methods

The present analysis of prospectively collected data compared cesarean deliveries during 1976, 1986, 1996, and 2006 at John Radcliffe Hospital in Oxford, UK (n=3222). Pregnancy, delivery, and neonatal details were reviewed.

Results

The proportion of deliveries by cesarean in the second stage of labor increased from 0.5% (22/4464) in 1976 to 2.1% (124/5998) in 2006 (P<0.001). The proportion of cesarean deliveries during the second stage because of failed instrumental delivery also increased over the study period from 59.1% (13/22) in 1976 to 71.0% (88/124) in 2006. Compared with cesareans at other stages, uterine trauma (P<0.001), blood loss greater than 1000 mL (P=0.002), and blood transfusion (P=0.001) were more frequent in second‐stage cesarean delivery. Neonates delivered by second‐stage cesarean had lower Apgar scores (P<0.001 for 1‐min and 5‐min scores) and cord arterial pH values (P<0.001) than did those delivered by cesarean earlier in labor. A trend towards an increase in neonatal trauma with second‐stage cesarean compared with cesarean delivery before labor or during the first stage did not reach statistical significance.

Conclusion

The proportion of deliveries by cesarean in the second stage of labor increased; these deliveries were associated with greater maternal and neonatal morbidity, but were not influenced by the indication for cesarean.
Perfect storm: Therapeutic plasma exchange for a patient with thyroid storm
Authors: McGonigle Andrea M. , Tobian Aaron A. R. , Zink Jennifer L. , King Karen E.
Published: June 2017

Thyroid storm is a potentially lethal complication of hyperthyroidism with increased thyroid hormones and exaggerated symptoms of thyrotoxicosis. First‐line therapy includes methimazole (MMI) or propylthiouracil (PTU) to block production of thyroid hormones as a bridge toward definitive surgical treatment. Untreated thyroid storm has a mortality rate of up to 30%; this is particularly alarming when patients cannot tolerate or fail pharmacotherapy, especially if they cannot undergo thyroidectomy. Therapeutic plasma exchange (TPE) is an ASFA category III indication for thyroid storm, meaning the optimum role of this therapy is not established, and there are a limited number of cases in the literature. Yet TPE can remove T3 and T4 bound to albumin, autoantibodies, catecholamines and cytokines and is likely beneficial for these patients. We report a patient with thyroid storm who could not tolerate PTU, subsequently failed therapy with MMI, and was not appropriate for thyroidectomy. TPE was therefore performed daily for 4 days (1.0 plasma volume with 5% albumin replacement and 2 U of plasma). Over the treatment course, the patient's thyroid hormones normalized and symptoms of thyroid storm largely resolved; his T3 decreased from 2.27 to 0.81 ng/mL (normal 0.8‐2.0), T4 decreased from 4.8 to 1.7 ng/mL (0.8‐1.8), heart rate normalized, altered mental status improved, and he converted to normal sinus rhythm. He was ultimately discharged in euthyroid state. He experienced no side effects from his TPE procedures. TPE is a safe and effective treatment for thyroid storm when conventional treatments are not successful or appropriate.
An Integrated Computational Framework to Assess the Mutational Landscape of α‐L‐Iduronidase IDUA Gene
Authors: Tanwar Himani , George Priya Doss C
Published: June 2017

Mucopolysaccharidosis type I is a lysosomal genetic disorder caused due to the deficiency of the α‐L‐iduronidase enzyme (IDUA). Mutations associated with IDUA lead to mild to severe forms of diseases characterized by different clinical features. In the present study, we first performed a comprehensive analysis using various in silico prediction tools to screen and prioritize the missense mutations or nonsynonymous SNPs (nsSNPs) associated with IDUA. Subsequently, statistical analysis was empowered to examine the predictive ability and accuracy of the in silico prediction tool results supporting the disease phenotype ranging from mild to severe. Till date, no study has been carried out in IDUA in analyzing the impact of the nsSNPs at the structural level. In this context with the aid of pathogenic and stability prediction in silico tools, we identified nsSNPs R89Q, R89W, and P533R to be most deleterious and disease‐causing having impact on the function of the protein. Extensive molecular dynamics analysis was performed using Gromacs to understand the deleterious nature of the mutants. Variations observed between the trajectory files of native and mutants R89Q, R89W, and P533R using Gromacs utilities enabled us to measure the adverse effects on the protein and could be the underlying reasons for the disease pathogenesis. These findings may be helpful in understanding the genotype‐phenotype relationship and molecular basis of the disease to design drugs for better treatment. J. Cell. Biochem. 119: 555–565, 2018. © 2017 Wiley Periodicals, Inc.
TGF‐β Stimulates Expression of Chondroitin Polymerizing Factor in Nucleus Pulposus Cells Through the Smad3, RhoA/ROCK1, and MAPK Signaling Pathways
Authors: Hu Bo , Xu Chen , Cao Peng , Tian Ye , Zhang Ying , Shi Changgui , Xu Jun , Yuan Wen , Chen Huajiang
Published: June 2017

The enzyme chondroitin polymerizing factor (ChPF) is primarily involved in extension of the chondroitin sulfate backbone required for the synthesis of sulfated glycosaminoglycan (sGAG). Transforming growth factor beta (TGF‐β) upregulates sGAG synthesis in nucleus pulposus cells; however, the mechanisms mediating this induction are incompletely understood. Our study demonstrated that ChPF expression was negatively correlated with the grade of degenerative intervertebral disc disease. Treatment of nucleus pulposus cells with TGF‐β induced ChPF expression and enhanced Smad2/3, RhoA/ROCK activation, and the JNK, p38, and ERK1/2 MAPK signaling pathways. Selective inhibitors of Smad2/3, RhoA or ROCK1/2, and knockdown of Smad3 and ROCK1 attenuated ChPF expression and sGAG synthesis induced by TGF‐β. In addition, we showed that RhoA/ROCK1 signaling upregulated ChPF via activation of the JNK pathway but not the p38 and ERK1/2 signaling pathways. Moreover, inhibitors of JNK, p38 and ERK1/2 activity also blocked ChPF expression and sGAG synthesis induced by TGF‐β in a Smad3‐independent manner. Collectively, our data suggest that TGF‐β stimulated the expression of ChPF and sGAG synthesis in nucleus pulposus cells through Smad3, RhoA/ROCK1 and the three MAPK signaling pathways. J. Cell. Biochem. 119: 566–579, 2018. © 2017 Wiley Periodicals, Inc.
An Infinite Family of Steiner Systems from Cyclic Codes
Authors: Ding Cunsheng
Published: June 2017

Steiner systems are a fascinating topic of combinatorics. The most studied Steiner systems are (Steiner triple systems), (Steiner quadruple systems), and . There are a few infinite families of Steiner systems in the literature. The objective of this paper is to present an infinite family of Steiner systems for all from cyclic codes. As a by‐product, many infinite families of 2‐designs are also reported in this paper.
T11TS immunotherapy repairs PI3K‐AKT signaling in T‐cells: Clues toward enhanced T‐cell survival in rat glioma model
Authors: Chaudhuri Suhnrita , Singh Manoj K. , Bhattacharya Debanjan , Datta Ankur , Hazra Iman , Mondal Somnath , Faruk Sk Md Omar , Ronsard Larance , Ghosh Tushar K. , Chaudhuri Swapna
Published: June 2017

Malignant glioma is the most fatal of astrocytic lineage tumors despite therapeutic advances. Onset and progression of gliomas is accompanied by severe debilitation of T‐cell defense and T‐cell survival. One of the chief contributors to T‐cell survival downstream of activation is the PI3K‐AKT pathway. Our prior studies showed that the novel immunotherapeutic molecule T11‐target structure (T11TS) blocks T‐cell apoptosis in glioma. We also showed activation of immunological synapse components and calcineurin‐NFAT pathway following T11TS immunotherapy of glioma‐bearing rats. This lead to investigations whether such T‐cell activation upon T11TS therapy translates into activation of downstream PI3K/AKT signals which may be related to observed blockade of T‐cell apoptosis. For the purpose, we assessed by flowcytometry and immunoblotting, expressions of PI3K, PDK1, AKT, p‐AKT, and PTEN in splenic T‐cells of normal, experimentally‐induced glioma‐bearing rats and glioma‐bearing rats receiving first, second and third doses of T11TS. We also determined comparative nuclear translocation of NF‐κB across groups. We found significant increases in T‐cell expressions of PDK1, PI3K, and p‐AKT in T11TS‐treated animal groups compared to sharp downregulations in glioma. AKT levels remained unchanged across groups. PTEN levels declined sharply after T11TS immunotherapy. T11TS also caused enhanced NF‐κB translocation to the T‐cell nucleus compared to glioma group. Results showed heightened activation of the PI3K‐AKT pathway in glioma‐bearing rats following T11TS immunotherapy. These results illustrate the novel role of T11TS immunotherapy in ameliorating the PI3K pathway in T‐cells in glioma‐bearing animals to enhance T‐cell survival, according greater defense against glioma. The study thus has far‐reaching clinical outcomes.
Angiogenesis biomarkers and their targeting ligands as potential targets for tumor angiogenesis
Authors: Mashreghi Mohammad , Azarpara Hassan , Bazaz Mahere R. , Jafari Arash , Masoudifar Aria , Mirzaei Hamed , Jaafari Mahmoud R.
Published: June 2017

Angiogenesis is known as one of the hallmarks in cancer which could play a key role in providing oxygen and nutrients for tumor cells. It has been shown that tumor cannot grow without sufficient development of new blood vessels. Accordingly, targeting angiogenesis, especially endothelial cells, could be considered as a common therapeutic target in tumors and more investigation on already existing biomarkers and potentially new biomarkers of endothelial cells seems to be necessary in cancer therapy. Moreover, the use of effective targeting approaches such as proteins and peptides, aptamers, and small molecules is an important step for targeting biomarkers associated with endothelial cells and angiogenesis in cancer therapy. These agents are FDA approved, or are currently under investigation in pre‐clinical and clinical studies. Among various biomarkers for angiogenesis microRNAs are suitable candidates for target therapy. These molecules play key roles in tumor angiogenesis which exert their effect via targeting a variety of cellular and molecular pathways involved in tumor angiogenesis. Here, we summarize a variety of biomarkers which their expressions or their functions could change the function of endothelial cells in tumor microenvironments. Moreover, we highlighted various therapeutic agents which could target these biomarkers.
Potential therapeutic interventions for chronic kidney disease‐associated sarcopenia via indoxyl sulfate‐induced mitochondrial dysfunction
Authors: Enoki Yuki , Watanabe Hiroshi , Arake Riho , Fujimura Rui , Ishiodori Kana , Imafuku Tadashi , Nishida Kento , Sugimoto Ryusei , Nagao Saori , Miyamura Shigeyuki , Ishima Yu , Tanaka Motoko , Matsushita Kazutaka , Komaba Hirotaka , Fukagawa Masafumi , Otagiri Masaki , Maruyama Toru
Published: June 2017

Background

Chronic kidney disease (CKD) patients experience skeletal muscle wasting and decreased exercise endurance. Our previous study demonstrated that indoxyl sulfate (IS), a uremic toxin, accelerates skeletal muscle atrophy. The purpose of this study was to examine the issue of whether IS causes mitochondria dysfunction and IS‐targeted intervention using AST‐120, which inhibits IS accumulation, or mitochondria‐targeted intervention using L‐carnitine or teneligliptin, a dipeptidyl peptidase‐4 inhibitor which retains mitochondria function and alleviates skeletal muscle atrophy and muscle endurance in chronic kidney disease mice.

Methods

The in vitro effect of IS on mitochondrial status was evaluated using mouse myofibroblast cells (C2C12 cell). The mice were divided into sham or 5/6‐nephrectomized (CKD) mice group. Chronic kidney disease mice were also randomly assigned to non‐treatment group and AST‐120, L‐carnitine, or teneligliptin treatment groups.

Results

In C2C12 cells, IS induced mitochondrial dysfunction by decreasing the expression of PGC‐1α and inducing autophagy in addition to decreasing mitochondrial membrane potential. Co‐incubation with an anti‐oxidant, ascorbic acid, L‐carnitine, or teneligliptine restored the values to their original state. In CKD mice, the body and skeletal muscle weights were decreased compared with sham mice. Compared with sham mice, the expression of interleukin‐6 and atrophy‐related factors such as myostatin and atrogin‐1 was increased in the skeletal muscle of CKD mice, whereas muscular Akt phosphorylation was decreased. In addition, a reduced exercise capacity was observed for the CKD mice, which was accompanied by a decreased expression of muscular PCG‐1α and increased muscular autophagy, as reflected by decreased mitochondria‐rich type I fibres. An AST‐120 treatment significantly restored these changes including skeletal muscle weight observed in CKD mice to the sham levels accompanied by a reduction in IS levels. An L‐carnitine or teneligliptin treatment also restored them to the sham levels without changing IS level.

Conclusions

Our results indicate that IS induces mitochondrial dysfunction in skeletal muscle cells and provides a potential therapeutic strategy such as IS‐targeted and mitochondria‐targeted interventions for treating CKD‐induced muscle atrophy and decreased exercise endurance.
Cerebrolysin prevents deficits in social behavior, repetitive conduct, and synaptic inhibition in a rat model of autism
Authors: Cuevas‐Olguin Roberto , Roychowdhury Swagata , Banerjee Anwesha , Garcia‐Oscos Francisco , Esquivel‐Rendon Eric , Bringas María Elena , Kilgard Michael P. , Flores Gonzalo , Atzori Marco
Published: June 2017

Autism spectrum disorder (ASD) is a syndrome of diverse neuropsychiatric diseases of growing incidence characterized by repetitive conduct and impaired social behavior and communication for which effective pharmacological treatment is still unavailable. While the mechanisms and etiology of ASD are still unknown, a consensus is emerging about the synaptic nature of the syndrome, suggesting a possible avenue for pharmacological treatment with synaptogenic compounds. The peptidic mixture cerebrolysin (CBL) has been successfully used during the last three decades in the treatment of stroke and neurodegenerative disease. Animal experiments indicate that at least one possible mechanism of action of CBL is through neuroprotection and/or synaptogenesis. In the present study, we tested the effect of CBL treatment (daily injection of 2.5 mL/Kg i.p. during 15 days) on a rat model of ASD. This was based on the offspring (43 male and 51 female pups) of a pregnant female rat injected with valproic acid (VPA, 600 mg/Kg) at the embryonic day 12.5, which previous work has shown to display extensive behavioral, as well as synaptic impairment. Comparison between saline vs. CBL‐injected VPA animals shows that CBL treatment improves behavioral as well as synaptic impairments, measured by behavioral performance (social interaction, Y‐maze, plus‐maze), maximal response of inhibitory γ‐amino butyric acid type A receptor (GABAAR)‐mediated synaptic currents, as well as their kinetic properties and adrenergic and muscarinic modulation. We speculate that CBL might be a viable and effective candidate for pharmacological treatment or co‐treatment of ASD patients. © 2017 Wiley Periodicals, Inc.
Implementation and clinical characteristics of a posttraumatic stress disorder brain collection
Authors: Mighdoll Michelle I. , Deep‐Soboslay Amy , Bharadwaj Rahul A. , Cotoia John A. , Benedek David M. , Hyde Thomas M. , Kleinman Joel E.
Published: June 2017

A postmortem human brain collection to study posttraumatic stress disorder (PTSD) is critical for uncovering the molecular mechanisms that contribute to this psychiatric disorder. We describe here the PTSD brain collection at the Lieber Institute for Brain Development in Baltimore, Maryland, consisting of postmortem brain donations acquired between 2012 and 2017. Thus far, 87 brains from individuals meeting DSM‐5 criteria for PTSD were collected after consent was obtained from legal next‐of‐kin, and subsequently clinically characterized for molecular studies. PTSD brain donors had high rates of comorbid diagnoses, including depression (62.1%), substance abuse (74.7%), drug‐related death (69.0%), and suicide completion (17.2%). PTSD cases were subdivided into two categories: combat‐related PTSD (n = 24) and noncombat/domestic PTSD (n = 63). The major differences between the combat‐related and domestic PTSD cohorts were sex, drug‐related death, and the prevalence of bipolar disorder (BPD) comorbidity. The combat‐related group was entirely male, with only one BPD subject (4.2%), and had significantly fewer drug‐related deaths (45.8%) in contrast to the domestic group (31.8% male, 36.5% bipolar, and 77.8% drug‐related deaths). Medical examiners' offices, particularly in areas with higher military populations, are an excellent source for PTSD brain donations of both combat‐related and domestic PTSD.
Spatial gradients in climatic trends across the southeastern Antilles 1980–2014
Authors: Jury Mark R.
Published: June 2017

ABSTRACT

Climatic trends in the southeastern Antilles island chain are analysed via reanalysis datasets in the period 1980–2014. Although a homogeneous marine climate surrounds these small islands embedded in northeast trade winds, the analysis presented here reveals spatial gradients in climatic trends during the satellite era. In the axis of the fresh North Brazil Current, sea surface temperature (SST) trends are steep (+0.04 °C year−1) and correspond with weaker winds and rising ozone concentrations (+0.15 DU year−1). Subsidence and meridional wind trends are related to an acceleration in the Hadley overturning atmospheric circulation which heats the trade wind inversion. Expanded wind shadows induce warmer SST, greater latent heat flux and deeper convection west of the Antilles islands. While rainfall has decreased in Trinidad and eastern Venezuela, the mountainous islands of Guadeloupe, Dominica and Martinique have increasing rainfall (+0.02 mm day−1 year−1) in the satellite era. Weakening ocean currents near Grenada may reflect a diminishing of the global thermohaline meridional overturning circulation.
Why was the western Pacific subtropical anticyclone weaker in late summer after the 2015/2016 super El Niño?
Authors: Liu Boqi , Zhu Congwen , Su Jingzhi , Hua Lijuan , Duan Yihong
Published: June 2017

The western Pacific subtropical anticyclone (WPSA), which bridges the El Niño events and the East Asian summer monsoon, is generally enhanced in boreal summer after El Niño events. However, it becomes weaker in boreal late summer (July–August) of 2016, following the 2015/2016 super El Niño event, indicating failure of the previous experience. Our results suggest that the weaker WPSA in late summer 2016 is associated with the extinction of the Indian Ocean capacitor effect, presenting the cold sea surface temperature anomalies (SSTAs) in the western tropical Indian Ocean (WTIO) after the fast decaying of the 2015/2016 super El Niño in spring. Compared with the case in 1982/1983 and 1997/1998, both data analysis and numerical experiments indicate that the cold WTIO SSTAs could induce an anomalous zonal circulation, with its descending branch over the WTIO and the ascending branch over the western North Pacific (WNP). Afterwards, the thermal structure in the upper troposphere of the WNP is altered to enhance the local wave guide, which facilitate the equatorward propagation of the mid‐latitudinal wave train into the WNP. Consequently, the abnormal ascending over the WNP weaken the WPSA in conjunction with the anomaly of the upper‐tropospheric cyclone due to the southward intrusion of the wave train during late summer 2016. This implicates the possible influence of El Niño evolution in spring on the WPSA intensity in the subsequent summer.
Spatial and temporal analysis of extreme bioclimate conditions in Vojvodina, Northern Serbia
Authors: Basarin Biljana , Lukić Tin , Mesaroš Minučer , Pavić Dragoslav , Đorđević Jasmina , Matzarakis Andreas
Published: June 2017

Several indices, with focus on extreme climate and bioclimate events have been calculated and their trends (over 1961 to 2014) analyzed in order to identify possible changes in temperature‐related climate extremes over Vojvodina region, Northern Serbia. Physiologically equivalent temperature (PET) has been used for the assessment of bioclimatological extremes in Vojvodina. A number of indices for temperature extremes have been defined by CLIVAR (Climate Variability and Predictability) and they are modified in order to detect extremes in bioclimatological variables (PET). In this study, we used 11 PET indices. The results indicate that the whole area is dominated by significant increase in the frequency of warm conditions and significant decrease in the cold conditions. These results could indicate that the warming in Vojvodina could be due to the more pronounced and higher frequency of warm bioclimatological extreme conditions. The frequency and the duration of heat waves are increasing for the whole area, while the decrease in number and duration of cold waves is not so pronounced.
Neoadjuvant chemoradiotherapy of pancreatic cancer induces a favorable immunogenic tumor microenvironment associated with increased major histocompatibility complex class I‐related chain A/B expression
Authors: Murakami Takashi , Homma Yuki , Matsuyama Ryusei , Mori Ryutaro , Miyake Kentaro , Tanaka Yusaku , Den Kanechika , Nagashima Yoji , Nakazawa Masatoshi , Hiroshima Yukihiko , Ueda Michio , Tanaka Kuniya , Hoffman Robert M. , Bouvet Michael , Endo Itaru
Published: June 2017

Background

Damage‐associated molecular patterns (DAMPs) are related to immune responses in malignant tumors including tumor‐infiltrating lymphocytes (TILs). The aim of the present study was to determine the relationship between expression of components of DAMPs and TILs in pancreatic cancer patients who underwent neoadjuvant chemoradiotherapy (NACRT) versus those who did not.

Methods

NACRT was administered to 51 patients with borderline‐resectable pancreatic cancer and not to 33 patients with resectable pancreatic cancer. Resected specimens were analyzed for the presence of DAMPs, major histocompatibility complex class I‐related chain A/B (MICA/B), and CD8+ TILs, CD4+ TILs, and forkhead box P3 positive (Foxp3+) TILs. The Treg/TIL ratio was obtained by dividing the number of Foxp3+ TILs, a surrogate for regulatory T cells, by the sum of CD8+ and CD4+ TILs.

Results

Overexpression of calreticulin, Hsp70, and MICA/B were all significantly correlated with NACRT administration. In the NACRT group, high MICA/B expression was associated with a low Treg/TIL ratio, indicating a favorable immunogenic tumor microenvironment. Patients with a lower Treg/TIL ratio had longer survival.

Conclusions

Overexpression of MICA/B, a component of DAMPs induced by NACRT, may play an important role in acquiring a favorable immune response for pancreatic cancer which contributes to longer survival, suggesting the potential of immunotherapy of this recalcitrant disease, especially for patients with overexpression of DAMPs.
Interval between cytoreductions as a marker of tumor biology in selecting patients for repeat cytoreductive surgery with hyperthermic intraperitoneal chemotherapy
Authors: Konstantinidis Ioannis T. , Levine Edward A. , Chouliaras Konstantinos , Russell Gregory , Shen Perry , Votanopoulos Konstantinos I.
Published: June 2017

Background and Objectives

Repeat cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) for recurrence of peritoneal surface malignancies is safe and effective. Patient selection and factors associated with a favorable outcome are still evolving.

Methods

A prospectively maintained institutional database consisting of 1314 CRS/HIPEC procedures performed between February 1993 and December 2015 was reviewed. Clinicopathologic data from 103 patients and 112 (8.5%) repeat CRS/HIPEC procedures were retrospectively analyzed.

Results

Primary tumors were appendiceal for 60 patients (58.3%), mesothelioma for 14 (13.6%), colorectal for 9 (8.7%), ovarian for 8 (7.8%). R0/R1 resection was achieved in 46 (46.5%) patients. The time interval between the initial and the repeat CRS/HIPEC was <1 year for 21 (20.4%), 1‐2 years for 40 (38.8%), and >2 years for 42 patients (40.8%). Overall median survival was 4.3 years and correlated with the time interval (1.3 years for <1 years, 3.7 years for 1‐2 years, and 7 years for >2 years; P < 0.001). In multivariate analysis, the R status (P = 0.005) and a time interval of more than 2 years (P = 0.0002) were strongly associated with survival with each additional month between the surgeries conferring a 2.6% reduction in the risk of death.

Conclusions

The current series validates time interval between cytoreductions as a major surrogate of tumor biology in selection of patients with recurrent peritoneal surface malignancies for repeat CRS/HIPEC. Complete repeat cytoreduction more than 2 years from the initial surgery is associated with a favorable outcome.
Predictors of surgical quality for retroperitoneal sarcoma: Volume matters
Authors: Maurice Matthew J. , Yih Jessica M. , Ammori John B. , Abouassaly Robert
Published: June 2017

Background and Objectives

The volume‐outcome relationship is well recognized. We sought to investigate this relationship in retroperitoneal sarcoma (RPS) surgery.

Methods

Non‐metastatic RPS cases from 2004 to 2014 in the National Cancer Database were analyzed. Hospitals in the top 10th percentile for volume were defined as high‐volume. Outcomes were selected a priori based on their known prognostic significance, including surgery use, R0/R1 resection, and R0 resection. Volume‐outcome associations were assessed by univariate and multivariable analyses.

Results

Of 3141 RPS cases identified, 70.0% were managed surgically. Of these, 93.0% were R0/R1 resections, and 67.6% were R0 resections. Surgical management, R0/R1 resection, and R0 resection were each associated with improved overall survival (P < 0.001). Hospital volume was an independent predictor of surgical management, R0 resection, and R0/R1 resection. Patients treated at high‐volume centers had 1.9‐fold higher odds of undergoing surgical management (P < 0.001), 2.5‐fold higher odds of receiving a R0/R1 resection (P = 0.026), and 1.8‐fold higher odds of an R0 resection (P < 0.001). Academic setting predicted use of surgical management (P < 0.001) and R0/R1 resection (P = 0.015) but not R0 resection (P = 0.882).

Conclusions

High‐volume hospitals are significantly associated with surgery use and improved surgical outcomes. Consideration should be given to further centralization of RPS care.
The impact of the use of intraoperative radiotherapy on costs, travel time and distance for women with breast cancer in the Mexico City Metropolitan Area
Authors: Bargallo‐Rocha Juan Enrique , Soto‐Perez‐de‐Celis Enrique , Picó‐Guzmán Francisco Javier , Quintero‐Rodríguez Carlos Eduardo , Almog David , Santiago‐Concha Gabriel , Flores‐Balcazar Christian Haydee , Corona Jaime , Vazquez‐Romo Rafael , Villarreal‐Garza Cynthia , Mohar Alejandro
Published: June 2017

Background and Objectives

The low availability and poor access to external beam radiotherapy (EBRT) in developing countries makes it hard for women with breast cancer to receive breast conservation. We studied the effect of providing intraoperative radiotherapy (IORT) on the travel time, distance, and costs of in the Mexico City Metropolitan Area (MCMA).

Methods

Sixty‐nine patients treated between January 2013 and September 2014 were analyzed. Travel distance and transit time was calculated using Google Maps. The time and distance patients living in the MCMA treated with IORT would have spent if they had received EBRT was calculated. Cost analysis for each modality was performed.

Results

71% (n = 49) lived in the MCMA. Sixteen (33%) received additional EBRT and 33 (66%) received IORT only. Mean driving distance and transit time of those 33 women was 132.6 km (SD 25.7) and 66 min (SD 32.9). Patients from the MCMA receiving IORT alone avoided 990 visits, 43 700 km and 65 400 min in transit. IORT led to a 12% reduction in costs per patient.

Conclusions

By reducing costs and time needed for patients to receive radiotherapy, IORT could potentially enhance access to breast conservation in resource‐limited developing countries.
Novel nomogram combining depth of invasion and size can accurately predict the risk for regional nodal metastases for appendiceal neuroendocrine tumors (A‐NET)
Authors: Mosquera Catalina , Fitzgerald Timothy L. , Vora Haily , Grzybowski Marysia
Published: June 2017

Introduction

The need for regional lymphadenectomy for treating appendiceal neuroendocrine tumors (A‐NET) is determined by the risk of nodal metastasis. Current guidelines for A‐NET are solely based on tumor size.

Methods Patients with A‐NET from 1988 to 2012 were identified from the SEER registry. The depth of invasion was defined as limited to the lamina propria (LP), invading the muscularis propria (MP), and through the serosa (TS).

Results

A total of 418 patients were included; the majority were female, white, and node‐negative. On univariate and multivariable, the risk of nodal metastasis was associated with age, size, depth of invasion, and extent of surgery. The model predicted the likelihood of nodal metastasis, with an area under the curve of 0.89. On survival analysis, age and tumor size predicted the survival in A‐NET. In a Cox regression model, they continued to predict survival. These data were utilized to create a nomogram to predict the risk of nodal metastases.

Conclusion

This nomogram, accurately predicts the risk of regional nodal metastases in A‐NET. In addition to providing valuable information on risk for regional nodal metastases, the depth of invasion is also predictive of survival for A‐NET.
Evaluation of the 8th edition American Joint Commission on Cancer (AJCC) staging system for patients with intrahepatic cholangiocarcinoma: A surveillance, epidemiology, and end results (SEER) analysis
Authors: Kim Yuhree , Moris Dimitrios P. , Zhang Xu‐Feng , Bagante Fabio , Spolverato Gaya , Schmidt Carl , Dilhoff Mary , Pawlik Timothy M.
Published: June 2017

Background

The objective of this study was to assess the prognostic performance of American Joint Committee on Cancer (AJCC) 8th edition in patients with intrahepatic cholangiocarcinoma (ICC) using a cancer registry.

Methods

The Surveillance, Epidemiology, and End Results (SEER) cancer registry was queried to identify 1008 patients who underwent surgical resection of ICC during 1998‐2013. Kaplan‐Meier method and Cox proportional hazards regression models were used to analyze long‐term survival. The relative discriminative abilities were assessed using the Harrell's concordance index.

Results

Median patient age was 62 years and 47.6% of the patients were male. Most tumors were T1 or T2 (n = 413, 41.0% and n = 329, 32.6%, respectively) and 22.1% of patients had lymph node (LN) metastasis. Median tumor size was 5.5 cm. With a median follow‐up of 18 months, median survival was 27 months and 5‐year OS was 30.6%. The OS c‐index for the AJCC 8th staging system was 0.669, which was comparable with the c‐index for the 7th edition AJCC staging system (c‐index: 0.667); the AJCC 8th‐edition did provide more discrete stratification of patients.

Conclusions

The new AJCC 8th‐edition staging system for ICC was largely comparable to the 7th‐edition version and did not provide a marked improvement in overall prognostic discrimination.
Simultaneous extraction and determination of antibiotics in soils using a method based on quick, easy, cheap, effective, rugged, and safe extraction and liquid chromatography with tandem mass spectrometry
Authors: Meng Minghui , He Zeying , Xu Yaping , Wang Lu , Peng Yi , Liu Xiaowei
Published: June 2017

The increasing use of antibiotics has caused substantial environmental problems, which are a matter of great concern. The aim of this work was to develop a quick, easy, cheap, effective, rugged, and safe method for 20 antibiotic residues in soil. The developed method is based on extraction with acetonitrile and phosphate buffer, clean up with dispersive solid‐phase extraction adsorbent using primary secondary amine, octadecylsilane, followed by liquid chromatography with tandem mass spectrometry determination. We optimized different extraction methods and the ratio of cleanup adsorbents to achieve good recoveries at seven spiking levels that ranged from 61.4 to 118.9% with a relative standard deviation below 20% (n = 5). The method quantification limit was in the range of 2–5 μg/kg for most analytes. Good linear regression coefficients greater than 0.990 were obtained. This method was applied for the analysis of real agricultural soil samples, confirming the feasibility of the method.
The anatomical evolution of the thyroid cartilage from childhood to adulthood: A computed tomography evaluation
Authors: Glikson Eran , Sagiv Doron , Eyal Ana , Wolf Michael , Primov‐Fever Adi
Published: June 2017

Objective

To enhance knowledge and understanding of the laryngeal framework maturation in different age groups and genders.

Study Design

Cohort imaging study.

Setting

Tertiary academic referral center.

Methods

Computed tomography neck scans of 283 patients aged 8 to 20 years were studied. The interlaminae angle (ILA) of the thyroid cartilage at the level of the vocal folds, the anterior projection (angulation) of the thyroid cartilage (TC), and the degree of calcifications were evaluated and compared in sequential age groups of both genders.

Results

Neck scans of 171 males and 112 females were reviewed. The average ILA was 76.45° ± 14.2 and 94.25° ± 10.2 for males and females, respectively (P < 10–25). In the female group, the mean angle was relatively constant (91–970) in all age groups, whereas in the male groups the angle decreased with age (920–670) (r = −0.9, P < 0.005) The most significant decrease was measured in the 14‐ to 15‐year age group. The thyroid prominence was significantly more anteriorly angulated in males. The angle in the female age groups was constant (170.1°), and the angle in males decreased with age (161.47°) (P = 0.000008). Calcifications were more prominent at the posterior portion of the cartilage in both genders and increased with age.

Conclusion

Structural diversities of the TC begin in adolescent males because the thyroid cartilage grows anteriorly with a narrower ILA and with a greater anterior angulation. Our study shows that these changes, along with the degree of laryngeal cartilages calcification in both genders, occur as a continuum throughout puberty.

Level of Evidence

4. Laryngoscope, 127:E354–E358, 2017
Joining Dissimilar Materials with Pulsed Nanosecond Fiber Lasers
Authors: Gabzdyl Jack , Capostagno Daniel
Published: June 2017

Industrial use of nanosecond lasers for applications such as marking, engraving, cutting, and even micromachining is well known – however, the use of these sources for welding and joining is relatively new. Most applications of high‐peak‐power, short‐pulsed lasers tend to be related to material removal, so their use for joining is perhaps counterintuitive. However, the versatility afforded by master oscillator power amplifier (MOPA)‐based nanosecond fiber sources give unparalleled flexibility in terms of control of the output characteristics. These lasers can be used, for example, with high‐peak‐power nanosecond pulsed output with tunable pulse duration and high frequency‐modulated quasi‐continuous‐wave (QCW) modes, as well as operated as a more conventional continuous‐wave (CW) laser.
For Eternity: The Idea of Labeling by Light
Authors: Westdickenberg Benjamin
Published: June 2017

What do have shoes, brake callipers, Coke and cow earmarks in common? The permanent laser marking. Whether batch or charge number, best bevor date, official registration or further data – the production of consumer or industry products cannot be imagined without laser marking. With its unique performance laser marking guarantees extremely reliable, very flexible and automated markings for “eternity”. Numerous industries, as for example automotive, fashion and food industry as well as medical engineering perch on laser marking for identification, labeling, branding, product security and backtracking purposes.
Redesigning Medical Instruments Using 3D Metal Printing
Authors: Radig Guido F. R.
Published: June 2017

Additive manufacturing (AM) methods of 3D printing are increasingly opening up new paths in medical technology. Alex Berry, founder of Sutrue (cf. Interview, p. 20), and Richard Trimlett, consultant at the Royal Brompton Hospital, are focusing strategically on AM for applications in cardiology. Is it possible to improve the “golden hands” of an experienced heart surgeon? Yes, it is. Using the example of a machine for performing sutures during operations and a cardiac stabilizer for endoscopic heart operations, Sutrue shows how operations on the heart can be performed more safely. Heart operations are soon to become faster and safer. And there is even more good news: patients are recovering faster.
Small‐molecule AT2 receptor agonists
Authors: Hallberg Mathias , Sumners Colin , Steckelings U. Muscha , Hallberg Anders
Published: June 2017

The discovery of the first selective, small‐molecule ATR receptor (AT2R) agonist compound 21 (C21) (8) that is now extensively studied in a large variety of in vitro and in vivo models is described. The sulfonylcarbamate derivative 8, encompassing a phenylthiofen scaffold is the drug‐like agonist with the highest affinity for the AT2R reported to date (Ki = 0.4 nM). Structure‐activity relationships (SAR), regarding different biaryl scaffolds and functional groups attached to these scaffolds and with a particular focus on the impact of various para substituents displacing the methylene imidazole group of 8, are discussed. Furthermore, the consequences of migration of the methylene imidazole group and presumed structural requirements for ligands that are aimed as AT2R agonists (e.g. 8) or AT2R antagonists (e.g. 9), respectively, are briefly addressed. A summary of the pharmacological actions of C21 (8) is also presented.
Inhibitors of kallikrein‐related peptidases: An overview
Authors: Masurier Nicolas , Arama Dominique P. , El Amri Chahrazade , Lisowski Vincent
Published: June 2017

Kallikrein‐related peptidases (KLKs) are a family of 15 secreted serine proteases that are involved in various physiological processes. Their activities are subtly regulated by various endogenous inhibitors, ranging from metallic ions to macromolecular entities such as proteins. Furthermore, dysregulation of KLK activity has been linked to several pathologies, including cancer and skin and inflammatory diseases, explaining the numerous efforts to develop KLK‐specific pharmacological inhibitors as potential therapeutic agents. In this review, we focus on the huge repertoire of KLKs inhibitors reported to date with a special emphasis on the diversity of their molecular mechanisms of inhibition.