bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression Collagen I and III in Anterior Vaginal Women with and without Pelvic Organ Prolapse
Authors: Basyar Basyar , Irianta Trika , Rauf Syahrul
Published: May 2019

Objective: To find out the expression of collagen [ and III in the anterior vaginal wall of women with and without pelvic organ prolapse (POP).

Method: The research was a cross sect ional study, conducted in Dr. Wahidin Sudiro Husodo hospital and its networks from January 1, 2011 to April 1, 2012. The case group consisted of 35 women with POPlevel III and IV.The contro l group consisted of35 women without POP. The expression of collagen I and III were examined by immunohistochemical test with the stain ing of antibody of collagen I (mouse monoclonal collagen lab 90395 ) and the antibody collagen III (Mu167 4i).The data was then analyzed by using a computer statistic program with a significance level of 0.05.

Result: It was found that in the group of women with POP, there were 28 cases of expression collagen III (84%), which is significantly higher than in women without POP, found in only 20 cases (58.8%), with p=0.02. Meanwhile, in the group of POP, 9.1% of subjects showed moderate expre ssion of collagen I, significantly less compared to the expressio n in the contro l group (35.3%), with p=0.007. For the ratio of collagen I and III, the result was weak in women with POP(58.5% ) while in the control group, the result was high (85.7%).

Conclu sion: In terms of collagen I and III expression, there was no significant difference between the two groups.

Keywords: collagen I, collagen III, pelvic organ prolapse, vaginal wall
Dokazivanje nejednakosti korištenjem simetrija
Authors: Kovač Vjekoslav
Published: May 2019

Obradit ćemo jednu tehniku kojom se zadana nejednakost može lako dokazati zahvaljujući nekoj svojoj simetriji i to tako da se najprije dokaže njezina "lošija" varijanta, koja se potom "poboljša". Općenitu ideju obrazložit ćemo na nekoliko primjera iz raznih grana matematike.
Defining urban centres using alternative data sets
Authors: Moylan Emily , Sarkar Somwrita
Published: May 2019

In growing cities, the evolution of urban form is partially motivated in principle by travel distance benefits. Evidence from travel data can support the categorisation of activity organisation as monocentric, polycentric or dispersed. We consider centricity measures at a fine geographical scale for Sydney, Australia using two data sets: Census journey-to-work transit data and commute trips from Opal transit smartcards. Only a few top-order centres are detected, and there is a significant level of dispersed activity in areas that are not centres. Further, most top-order centres that are detected are clustered spatially. Thus, we find that a comparison of the data sets does not support the polycentric model but instead a legacy monocentric model combined with dispersal.
Design Of Web Based Employees Information System Design in SD Kumnamu School Tangerang
Authors: Rahayu Sri , Muhtadi Yudi , Al Farobie Abizal
Published: May 2019

ayroll systems in every company vary, most have used computer-based information systems, but there are still some companies that have not implemented it as in SD KUMNAMU SCHOOL. In this educational institution in the payroll information system is still using the calculation manually and using MS aids program. Excel. In this study using SWOT method as a method used to determine the strengths, weaknesses, opportunities, and system threats that run today through several stages of interview and literature study. Which produces a payroll information system that can manage computerized payroll, perform absentee calculations, automatically calculate monthly salary, allowances calculation, present salary slips and salary reports required every month or every year and others. System design using UML (Unified Modeling Language) tool, while in making system program using MySQL tool to design database and PHP (Hypertext Preprocessor) as programming language.
Analyze and Record a Series of Corporate Sales Transactions On Web Based Accounting Online System
Authors: Djatmiko M Budi , Husain Al , Maulani Giandari , Nirmalasari Leli
Published: May 2019

In the economic activities of the company can not be separated from the name of the process of sales and purchases. Especially in the company's accounting system sales process does not escape become part of the system. That's because sales become vital to prosper the company's welfare. As a financial revenue source in the company the sales process must be analyzed and recorded in real time whether wherever and whenever. As an anticipatory action to reduce the crime of financial acts such as manipulation at the company so as not to cause big losses to the company and result in bankruptcy of the company. Use of Web Based Accounting Online System or commonly known WBAOS it can all be done easily. Starting from analyzing company sales to record sales. This is considered very effective if using an accounting system that is still offline and more efficient of course.
The Effect of Online Consumer Review on the Intention of Buying Products on Social Commerce
Authors: Muslimah Nurul , Mursid Mansur Chadi
Published: May 2019

E-commerce is one form of evolution business models that adopt Web 2.0 technology with the aim of increasing consumer participation and gaining economic value ( greater economic value ) .This study aims to conduct confirmatory research on the relationship between social trade construction, online consumer review, trust and intention to buy through a questionnaire survey done to e-commerce users, especially students at Pekalongam IAIN using the purposive sampling method . The results of the collected questionnaires are then analyzed quantitatively using partial least square (PLS) . From the analysis and quantitative testing that can be done It was concluded that online consumer review does not have a direct influence on the intention to buy, but construction of trade has a direct influence on the buyer's trust and it is known that trust has a direct influence on the intention to buy.
Periodic Data Analysis and Forecasting As An Overview of Future Management Economics
Authors: Henderi Henderi , Zuliana Siti Ria , Pradana Restu Adi
Published: May 2019

In economics management is needed periodic data (time series) from production effort in predicting continuation of a situation is action which at one time must be done. For economic or political experts, it seems to be an obligation that must be carried out when they find a situation say just the economic crisis that befell a country with great, to provide predictive reviews about how the impact will be on the continuation of the existence of that country. So from that the aim of this research is to discuss about conceptual and conceptual aspects about periodic data, calculation of straight line trends through free method, half moving average, half average and least number of squares, non linear trend calculation which is trend parabola and exponential trends, calculations for changing trend equations into quarterly and monthly trends, calculations for changing trend equations into average trends, calculating seasonal variation values ​​through simple average methods, ratio to trend, ratio of moving averages and relative berangkai, and calculation of cyclic variation values ​​for annual and quarterly data. The method used during this study took place, namely using a literature study method which functions so that in research, researchers continue to add insight.
Análisis del proceso de manufactura mediante proceso CAD-CAM de un molde para materiales compuestos para la industria automotriz.
Authors: Sánchez Carrión Edgar Fabián , Castillo Cárdenas Edison Marcelo , Bravo Morocho Victor David , Abarca Pérez Edison Patricion , Montufar Paúl
Published: May 2019

El presente trabajo se analiza un proceso de construcción y las variables de un molde para un proceso de extrusión para material compuesto, el molde debe cumplir con características y tolerancias especificas ya que este es un proceso para la obtención de perfiles de sección constante en base a materiales compuestos por medio refuerzo de fibra de vidrio y de matriz termoestable, al servir estos moldes para la obtención de secciones constantes es necesario que el molde en su construcción cumpla con las consicioines de trabajo. Se estableció un estudio experimental de los mejores procesos de construcción del molde de sección constantes aplicando procesos de manufactura virtual, puesto que la constitución debe soportar las variables de trabajo como son la transferencia de calor, la fricción de las fibras de vidrio, y la velocidad de trabajo.
Akıllı Kent Bileşeni Olarak “Akıllı Vatandaş” Bağlamında Bir Test Sahası Olarak Üniversite Kampüsleri
Authors: GÜRSOY Oğuzhan , ÖMÜRGÖNÜLŞEN Uğur
Published: May 2019

Bu makalenin amacı, kurulum maliyetleri yüksek olan
akıllı kent projelerinde pilot uygulama gerçekleştirmenin önemini vurgulamak ve
akıllı kentin bileşenlerinden birisi olan “akıllı vatandaş” bileşeni temelinde
pilot projeler için üniversite kampüslerinin iyi bir uygulama alanı olabileceğini
göstermektir. Bu amaca ulaşmak için ilk olarak toplum ve teknoloji ilişkisi
gözetilerek sosyolojik bir analiz olan “kuşaksal farklılıklara” değinilmiş ve
üniversitelerin kent ve toplumla olan ilişkisi incelenmiştir. Daha sonra
üniversite kampüslerinin akıllı kent projelerinin test edilmesi ve topluma
tanıtılması noktasında sahip olduğu avantaj ve dezavantajlar
değerlendirilmiştir. Bisiklet ve araç paylaşımı gibi akıllı hareketlik
önlemlerinin uygulanması ve akıllı kent kültürünün oluşturulması için en ideal
yerlerden birisinin gençlerin hareketlilik sahası halindeki üniversite kampüsleri
olduğu sonucuna varılmıştır.
GAMBARAN TINGKAT KEPUASAN IBU YANG BERSALIN PADA BIDAN DAN DUKUN BAYI DI WILAYAH KERJA PUSKESMAS ARJASARI KABUPATEN BANDUNG
Authors: Noor Hayati Suci
Published: May 2019

Tingginya angka kematian ibu dan bayi di Indonesia terutama di Kota Bandung diakibatkan masih banyaknya pertolongan persalinan yang dilakukan oleh Dukun Bayi. Tujuan penelitian ini yaitu untuk mengetahui perbedaan tingkat kepuasan ibu yang bersalin di Wilayah Kerja Puskesmas Arjasari Kabupaten Bandung. Metode yang digunakan dalam penelitian ini yaitu deskriptif. Sampel berjumlah 75 orang, yang terdiri dari 35 orang ibu yang bersalin pada dukun bayi dan 40 orang ibu yang bersalin pada bidan, diambil dengan teknik simple random sampling. Analisa data dengan menggunakan analisis univariat. Hasil penelitian pada pertolongan persalinan yang dilakukan oleh Bidan berdasarkan analisis kuadran terdapat dua unsur pada kuadran II dan tiga unsur pada kuadran III. Tidak terdapat unsur pada kuadran I dan IV. Sedangkan pada pertolongan persalinan yang dilakukan oleh Dukun Bayi terdapat dua unsur pada Kuadran I, satu unsur pada kuadran II, satu unsur pada kuadran IIIÂ  dan satu unsur pada kuadran IV.
LITERATUR REVIEW : APLIKASI TERAPI HAN (HIPNOTIS, AKTIFITAS FISIK, NUTRISI) PADA KELUARGA ANAK USIA SEKOLAH DENGAN OBESITAS
Authors: Darmawati Irma
Published: May 2019

Tingginya angka kejadian obesitas pada anak usia sekolah di Indonesia disebabkan oleh adanya perubahan pola makan makanan cepat saji dan adanya perkembangan teknologi sebagai salah satu gaya hidup baru yang justru dapat menurunkan aktifitas anak. Optimalisasi peran keluarga menjadi sangat penting, karena keluarga adalah rumah pertama tempat anak belajar hidup sehat. Melalui upaya pemberian asuhan keperawatan keluarga diharapkan dapat mengelola masalah keluarga salah satunya pada anak usia sekolah. Pencarian literatur dilakukan dengan mencari kesamaan (compare), mencari ketidaksamaan (contrass), memberikan pandangan (criticize), membandingkan (synthesize), serta meringkas (summarize) materi-materi yang berkaitan dengan terapi yang dapat dilakukan pada anak usia sekolah dengan masalah obesitas dari berbagai bahan rujukan dengan rentang waktu penerbitan 2006-2015. Terapi HAN (Hipnosis, Aktivitas fisik, Nutrisi)Â  dapat diterapkan dalam proses asuhan keperawatan bagi keluarga binaan perawat dengan tujuan utama perubahan perilaku hidup sehat yang menunjang pada upaya pencapaian berat badan ideal bagi anak dan keluarga dengan masalah obesitas. Pendekatan terapi yang pertama, hipnosis dilakukan untuk memberikan sugesti positif pada anak terkait tubuh ideal dan pola hidup sehat. Pendekatan terapi yang kedua adalah terapi aktivitas fisik pada anak. Pendekatan terapi yang ketiga adalah terapi nutrisi. Terapi nutrisi ini dilakukan melalui pola makan food combining yang merupakan cara atau pola konsumsi makanan dengan memperhatikan jenis bahan makanan yang selaras sehingga dapat mengoptimalkan pencernaan dan penyerapan zat makanan. Penerapan terapi HAN ini dapat dijadikan sebagai inovasi perawat puskesmas yang akan melaksanakan kunjungan rumah sehingga dapat mengendalikan angka kejadian obesitas pada anak usia sekolah.
Gambaran Intensi Minum Obat Pencegah Filariasis Pada Ibu Rumah Tangga Di Desa Citalahab Kecamatan Karangjaya Kabupaten Tasikmalaya
Authors: Yuliani Elvin , Juniarti Neti , Yamin Ahmad
Published: May 2019

ABSTRAKÂ PENDAHULUAN: Program Pemberian Obat Pencegahan secara Massal (POPM) Filariasis di Indonesia dilaksanakan sebagai salah satu upaya memutuskan rantai penularan Filariasis di daerah endemi. Target cakupan POPM Filariasis ditetapkan sebesar 85%. Pada tahun 2015 cakupan minum obat terendah di wilayah Kabupaten Tasikmalaya berada di Desa Citalahab Kecamatan Karangjaya dengan persentase minum obat pencegahan sebesar 46,95% dari jumlah sasaran minum obat. Tujuan penelitian ini adalah untuk mengetahui gambaran intensi minum obat pencegah Filariasis pada ibu rumah tangga di Desa Citalahab Kecamatan Karangjaya Kabupaten Tasikmalaya. METODE PENELITIAN: Metode penelitian yang digunakan adalah cross sectional study. Teknik pengambilan sampel menggunakan metode simple random sampling dengan jumlah sampel sebanyak 166 orang responden. Lokasi penelitian dilakukan di Desa Citalahab Kecamatan Karangjaya Kabupaten Tasikmalaya. Pengumpulan data menggunakan kuesioner yang mengukur intensi. Analisis data disajikan dalam bentuk distribusi frekuensi. KESIMPULAN: Hasil penelitian menunjukan Â intensi minum obat pencegah Filariasis pada ibu rumah tangga di Desa Citalahab Kecamatan Karangjaya masih rendah.Â Â ABSTRACTINTRODUCTION: Mass Drug Administration (MDA) Program of Lymphatic Filariasis Â Â in Indonesia was implemented as an effort to break the chain of transmission of Filariasis in endemic areas. Target coverage of MDA is set at 85%. In 2015, the lowest drug coverage in Tasikmalaya Regency was in Citalahab Village, Karangjaya District with the percentage of MDA coverage (46.95%) from the target.. The purpose of this research was to explore the description of intention to mass drug administration of Lymphatic Filariasis in housewife in Citalahab village, Karangjaya sub-district, Tasikmalaya regency. RESEARCH METHOD: The research method used is cross sectional study. The sampling technique used simple random sampling method with 166 respondents. The research location was done in Citalahab Village, Karangjaya Sub-district, Tasikmalaya Regency. Data collection uses questionnaires that measure intentions. Data analysis was presented in the form of frequency distribution. CONCLUSIONS: The results showed the intention of taking the drug of prevention of filariasis in housewife in Citalahab Village, Karangjaya Sub-district is still low
Capecitabine Induced Hand-Foot Syndrome: A Systematic Review of Case Reports
Authors: ARAS Elif , YUCEL Kamer Tecen , EKİNCİOGLU Aygin Bayraktar , GULLU İbrahim
Published: May 2019

Objective: Capecitabine, a prodrug of 5-fluorouracil, is currently used in the treatment of metastatic colorectal and breast cancers. The aim of this study was to review the pharmacological mechanisms, treatment strategies, and documented case reports of capecitabine-induced hand–foot syndrome (HFS).Methods: All case reports documented in the PubMed, Web of Science, and Scopus databases up to February 2018 were searched and reviewed using the keywords capecitabine, hand-foot syndrome, and case report.Results: The database search identified 373 articles in the literature; of these, 88 articles (having 111 case reports) in the English or Turkish language having a full-text access were included in the study. The median duration of capecitabine-induced HFS was 28 (range, 7–140) days, and the daily dose of capecitabine ranged between 850 and 5000 mg/m2 in cases wherein capecitabine was applied as monotherapy(n=19). A dose reduction or treatment discontinuation, systemic or topical treatment alone or in combination, and the use of henna, vitamin E, or pyridoxine were preferred options in the treatment of HFS.Conclusion: Health care providers and patients should be aware of developing capecitabine-induced HFS and its risk factors. Early recognition and treatment initiation for HFS are important to maintain effective chemotherapy in patients with cancer.
USO DE PLANTAS DO DOMÍNIO CERRADO COM FINS MEDICINAIS EM URUTAÍ, GO, BRASIL
Authors: Marcelo Vanessa Gonzaga , Paixão Caroliny Fatima Chaves , Ramos Marcus Vinícius Vieitas
Published: May 2019

Estudos Etnobotânicos contribuem com informações que auxiliam na definição de práticas de uso e manejo sustentável das espécies vegetais. O objetivo deste trabalho foi levantar o conhecimento e o uso de plantas medicinais nativas do domínio Cerrado pela população de Urutaí, GO. Foram selecionados 100 informantes por meio de amostragens aleatórias, sendo efetuadas entrevistas estruturadas em suas residências. Além de informações sócio-econômicas, os participantes foram questionados sobre o conhecimento e utilização de espécies nativas do domínio Cerrado para cura ou prevenção de doenças. Foi determinada a diversidade do uso pelo índice de Shannon-Wiener e a concordância de uso popular corrigida (CUPc), sendo a última calculada para as plantas medicinais citadas por três ou mais informantes e com valor de concordância quanto ao uso popular (CUP) maior que 20%. Não houve relação do conhecimento de plantas medicinais nativas do cerrado com sexo, idade, escolaridade e procedência (rural ou urbana), de acordo com os testes estatísticos aplicados. Os entrevistados citaram 37 espécies do domínio Cerrado com uso medicinal, sendo estas espécies distribuídas em 26 famílias botânicas. A diversidade do uso das espécies nativas foi baixa (H’= 3,21) quando comparada com outros trabalhos.  A maioria das espécies nativas citadas é de hábito arbóreo e são predominantemente encontradas em formações florestais e savânicas variantes do domínio Cerrado. Entre as espécies estudadas, sucupira e cana-de-macaco se destacaram por apresentarem maiores valores de concordância quanto ao uso fitoterapêutico popular corrigida (CUPc).
A Variable Block Insertion Heuristic for Solving Permutation Flow Shop Scheduling Problem with Makespan Criterion
Authors: Kizilay Damla , Tasgetiren Mehmet Fatih , Pan Quan-Ke , Gao Liang
Published: May 2019

In this paper, we propose a variable block insertion heuristic (VBIH) algorithm to solve the permutation flow shop scheduling problem (PFSP). The VBIH algorithm removes a block of jobs from the current solution. It applies an insertion local search to the partial solution. Then, it inserts the block into all possible positions in the partial solution sequentially. It chooses the best one amongst those solutions from block insertion moves. Finally, again an insertion local search is applied to the complete solution. If the new solution obtained is better than the current solution, it replaces the current solution with the new one. As long as it improves, it retains the same block size. Otherwise, the block size is incremented by one and a simulated annealing-based acceptance criterion is employed to accept the new solution in order to escape from local minima. This process is repeated until the block size reaches its maximum size. To verify the computational results, mixed integer programming (MIP) and constraint programming (CP) models are developed and solved using very recent small VRF benchmark suite. Optimal solutions are found for 108 out of 240 instances. Extensive computational results on the VRF large benchmark suite show that the proposed algorithm outperforms two variants of the iterated greedy algorithm. 236 out of 240 instances of large VRF benchmark suite are further improved for the first time in this paper. Ultimately, we run Taillard’s benchmark suite and compare the algorithms. In addition to the above, three instances of Taillard’s benchmark suite are also further improved for the first time in this paper since 1993.
In Vitro Antioxidant, Antityrosinase, and Cytotoxic Activities of Astaxanthin from Shrimp Waste
Authors: Chintong Sutasinee , Phatvej Wipaporn , Rerk-Am Ubon , Waiprib Yaowapha , Klaypradit Wanwimol
Published: May 2019

Astaxanthin is a potent antioxidant compared with vitamins and other antioxidants. However, astaxanthin extract from shrimp processing waste has not yet been used in cosmetic products. This study aimed to explore the natural astaxanthin from shrimp shells for antioxidant and antityrosinase activities as well as potential toxicity. The antioxidant activities were performed with 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging, β-carotene bleaching, and singlet oxygen quenching assays. The results revealed that astaxanthin extract demonstrated potent antioxidant activities against DPPH and ABTS radicals, and prevented the bleaching of β-carotene and quenching of singlet oxygen (EC50 17.5 ± 3.6, 7.7 ± 0.6, 15.1 ± 1.9 and 9.2 ± 0.5 μg/mL, respectively). Furthermore, the astaxanthin extract could inhibit tyrosinase activity (IC50 12.2 ± 1.5 μg/mL) and had no toxic effects on human dermal fibroblast cells. These results suggested that shrimp astaxanthin would be a promising dietary supplement for skin health applications.
Lessons from Inter-Comparison of Decadal Climate Simulations and Observations for the Midwest U.S. and Great Lakes Region
Authors: Sharma Ashish , Hamlet Alan F. , Fernando Harindra J.S.
Published: May 2019

Even with advances in climate modeling, meteorological impact assessment remains elusive, and decision-makers are forced to operate with potentially malinformed predictions. In this article, we investigate the dependence of the Weather Research and Forecasting (WRF) model simulated precipitation and temperature at 12- and 4-km horizontal resolutions and compare it with 32-km NARR data and 1/16th-degree gridded observations for the Midwest U.S. and Great Lakes region from 1991 to 2000. We used daily climatology, inter-annual variability, percentile, and dry days as metrics for inter-comparison for precipitation. We also calculated the summer and winter daily seasonal minimum, maximum, and average temperature to delineate the temperature trends. Results showed that NARR data is a useful precipitation product for mean warm season and summer climatological studies, but performs extremely poorly for winter and cold seasons for this region. WRF model simulations at 12- and 4-km horizontal resolutions were able to capture the lake-effect precipitation successfully when driven by observed lake surface temperatures. Simulations at 4-km showed negative bias in capturing precipitation without convective parameterization but captured the number of dry days and 99th percentile precipitation extremes well. Overall, our study cautions against hastily pushing for increasingly higher resolution in climate studies, and highlights the need for the careful selection of large-scale boundary forcing data.
Recovery of Cobalt from Spent Lithium-Ion Mobile Phone Batteries Using Liquid–Liquid Extraction
Authors: Quintero-Almanza Daniel , Gamiño-Arroyo Zeferino , Sánchez-Cadena Lorena Eugenia , Gómez-Castro Fernando Israel , Uribe-Ramírez Agustín Ramón , Aguilera-Alvarado Alberto Florentino , Ocampo Carmona Luz Marina
Published: May 2019

The aim of this paper was to propose and test a continuous cobalt recovery process from waste mobile phone batteries. The procedure started with dismantling, crushing, and classifying the materials. A study on leaching with sulfuric acid and hydrogen peroxide was carried out with subsequent selective separation of cobalt by means of liquid–liquid extraction. The best extraction conditions were determined based on a sequence of experiments that consisted of selecting the best extractant for cobalt, then assessing the impact of extractant concentration, pH, and contact time on the extraction yield. With these conditions, an extraction isotherm was obtained and correlated with a mathematical model to define the number of extraction stages for a countercurrent process using the McCabe–Thiele method. Then, a similar study was done for stripping conditions and, as a last step, cobalt electroplating was performed. The proposed process offers a solution for the treatment of these batteries, avoiding potential problems of contamination and risk for living beings, as well as offering an opportunity to recover valuable metal.
The Emerging Role of Blockchain Technology Applications in Routine Disease Surveillance Systems to Strengthen Global Health Security
Authors: Chattu Vijay Kumar , Nanda Anjali , Chattu Soosanna Kumary , Kadri Syed Manzoor , Knight Andy W
Published: May 2019

Blockchain technology has an enormous scope to revamp the healthcare system in many ways as it improves the quality of healthcare by data sharing among all the participants, selective privacy and ensuring data safety. This paper explores the basics of blockchain, its applications, quality of experience and advantages in disease surveillance over the other widely used real-time and machine learning techniques. The other real-time surveillance systems lack scalability, security, interoperability, thus making blockchain as a choice for surveillance. Blockchain offers the capability of enhancing global health security and also can ensure the anonymity of patient data thereby aiding in healthcare research. The recent epidemics of re-emerging infections such as Ebola and Zika have raised many concerns regarding health security which resulted in strengthening the surveillance systems. We also discuss how blockchains can help in identifying the threats early and reporting them to health authorities for taking early preventive measures. Since the Global Health Security Agenda addresses global public health threats (both infectious and NCDs); strengthen the workforce and the systems; detect and respond rapidly and effectively to the disease threats; and elevate global health security as a priority. The blockchain has enormous potential to disrupt many current practices in traditional disease surveillance and health care research.
Mitochondrial Dysfunction in the Aging Retina
Authors: Eells Janis T.
Published: May 2019

Mitochondria are central in retinal cell function and survival and they perform functions that are critical to cell function. Retinal neurons have high energy requirements, since large amounts of ATP are needed to generate membrane potentials and power membrane pumps. Mitochondria over the course of aging undergo a number of changes. Aged mitochondria exhibit decreased rates of oxidative phosphorylation, increased reactive oxygen species (ROS) generation and increased numbers of mtDNA mutations. Mitochondria in the neural retina and the retinal pigment epithelium are particularly susceptible to oxidative damage with aging. Many age-related retinal diseases, including glaucoma and age-related macular degeneration, have been associated with mitochondrial dysfunction. Therefore, mitochondria are a promising therapeutic target for the treatment of retinal disease.
Mitochondrial Dysfunction and Multiple Sclerosis
Authors: Barcelos Isabella Peixoto de , Troxell Regina M. , Graves Jennifer S.
Published: May 2019

In recent years, several studies have examined the potential associations between mitochondrial dysfunction and neurodegenerative diseases such as multiple sclerosis (MS), Parkinson’s disease and Alzheimer’s disease. In MS, neurological disability results from inflammation, demyelination, and ultimately, axonal damage within the central nervous system. The sustained inflammatory phase of the disease leads to ion channel changes and chronic oxidative stress. Several independent investigations have demonstrated mitochondrial respiratory chain deficiency in MS, as well as abnormalities in mitochondrial transport. These processes create an energy imbalance and contribute to a parallel process of progressive neurodegeneration and irreversible disability. The potential roles of mitochondria in neurodegeneration are reviewed. An overview of mitochondrial diseases that may overlap with MS are also discussed, as well as possible therapeutic targets for the treatment of MS and other neurodegenerative conditions.
Recent Advancements in Doped/Co-Doped Carbon Quantum Dots for Multi-Potential Applications
Authors: Kandasamy Ganeshlenin
Published: May 2019

Carbon quantum dots (CQDs)/carbon nanodots are a new class of fluorescent carbon nanomaterials having an approximate size in the range of 2–10 nm. The majority of the reported review articles have discussed about the development of the CQDs (via simple and cost-effective synthesis methods) for use in bio-imaging and chemical-/biological-sensing applications. However, there is a severe lack of consolidated studies on the recently developed CQDs (especially doped/co-doped) that are utilized in different areas of application. Hence, in this review, we have extensively discussed about the recent development in doped and co-doped CQDs (using elements/heteroatoms—e.g., boron (B), fluorine (F), nitrogen (N), sulphur (S), and phosphorous (P)), along with their synthesis method, reaction conditions, and/or quantum yield (QY), and their emerging multi-potential applications including electrical/electronics (such as light emitting diode (LED) and solar cells), fluorescent ink for anti-counterfeiting, optical sensors (for detection of metal ions, drugs, and pesticides/fungicides), gene delivery, and temperature probing.
The Key Roles of PTEN in T-Cell Acute Lymphoblastic Leukemia Development, Progression, and Therapeutic Response
Authors: Martelli Alberto M. , Paganelli Francesca , Fazio Antonietta , Bazzichetto Chiara , Conciatori Fabiana , McCubrey James A.
Published: May 2019

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive blood cancer that comprises 10–15% of pediatric and ~25% of adult ALL cases. Although the curative rates have significantly improved over the past 10 years, especially in pediatric patients, T-ALL remains a challenge from a therapeutic point of view, due to the high number of early relapses that are for the most part resistant to further treatment. Considerable advances in the understanding of the genes, signaling networks, and mechanisms that play crucial roles in the pathobiology of T-ALL have led to the identification of the key drivers of the disease, thereby paving the way for new therapeutic approaches. PTEN is critical to prevent the malignant transformation of T-cells. However, its expression and functions are altered in human T-ALL. PTEN is frequently deleted or mutated, while PTEN protein is often phosphorylated and functionally inactivated by casein kinase 2. Different murine knockout models recapitulating the development of T-ALL have demonstrated that PTEN abnormalities are at the hub of an intricate oncogenic network sustaining and driving leukemia development by activating several signaling cascades associated with drug-resistance and poor outcome. These aspects and their possible therapeutic implications are highlighted in this review.
Role of c-MET Inhibitors in Overcoming Drug Resistance in Spheroid Models of Primary Human Pancreatic Cancer and Stellate Cells
Authors: Firuzi Omidreza , Che Pei Pei , El Hassouni Btissame , Buijs Mark , Coppola Stefano , Löhr Matthias , Funel Niccola , Heuchel Rainer , Carnevale Ilaria , Schmidt Thomas , Mantini Giulia , Avan Amir , Saso Luciano , Peters Godefridus J. , Giovannetti Elisa
Published: May 2019

Pancreatic stellate cells (PSCs) are a key component of tumor microenvironment in pancreatic ductal adenocarcinoma (PDAC) and contribute to drug resistance. c-MET receptor tyrosine kinase activation plays an important role in tumorigenesis in different cancers including PDAC. In this study, effects of PSC conditioned medium (PCM) on c-MET phosphorylation (by immunocytochemistry enzyme-linked immunosorbent assay (ELISA)) and drug response (by sulforhodamine B assay) were investigated in five primary PDAC cells. In novel 3D-spheroid co-cultures of cyan fluorescence protein (CFP)-firefly luciferase (Fluc)-expressing primary human PDAC cells and green fluorescence protein (GFP)-expressing immortalized PSCs, PDAC cell growth and chemosensitivity were examined by luciferase assay, while spheroids’ architecture was evaluated by confocal microscopy. The highest phospho-c-MET expression was detected in PDAC5 and its subclone sorted for “stage specific embryonic antigen-4” (PDAC5 (SSEA4)). PCM of cells pre-incubated with PDAC conditioned medium, containing increased hepatocyte growth factor (HGF) levels, made PDAC cells significantly more resistant to gemcitabine, but not to c-MET inhibitors. Hetero-spheroids containing both PSCs and PDAC5 (SSEA4) cells were more resistant to gemcitabine compared to PDAC5 (SSEA4) homo-spheroids. However, c-MET inhibitors (tivantinib, PHA-665752 and crizotinib) were equally effective in both spheroid models. Experiments with primary human PSCs confirmed the main findings. In conclusion, we developed spheroid models to evaluate PSC–PDAC reciprocal interaction, unraveling c-MET inhibition as an important therapeutic option against drug resistant PDAC.
Active Targeting Strategies Using Biological Ligands for Nanoparticle Drug Delivery Systems
Authors: Yoo Jihye , Park Changhee , Yi Gawon , Lee Donghyun , Koo Heebeom
Published: May 2019

Targeting nanoparticle (NP) carriers to sites of disease is critical for their successful use as drug delivery systems. Along with optimization of physicochemical properties, researchers have focused on surface modification of NPs with biological ligands. Such ligands can bind specific receptors on the surface of target cells. Furthermore, biological ligands can facilitate uptake of modified NPs, which is referred to as ‘active targeting’ of NPs. In this review, we discuss recent applications of biological ligands including proteins, polysaccharides, aptamers, peptides, and small molecules for NP-mediated drug delivery. We prioritized studies that have demonstrated targeting in animals over in vitro studies. We expect that this review will assist biomedical researchers working with NPs for drug delivery and imaging.
Targeting Endometrial Cancer Stem Cell Activity with Metformin Is Inhibited by Patient-Derived Adipocyte-Secreted Factors
Authors: Kitson Sarah J. , Rosser Matthew , Fischer Deborah P. , Marshall Kay M. , Clarke Robert B. , Crosbie Emma J.
Published: May 2019

Advanced endometrial cancer continues to have a poor prognosis, due to limited treatment options, which may be further adversely impacted by obesity. Endometrial cancer stem cells have been reported to drive metastasis, chemotherapy resistance and disease relapse, but have yet to be fully characterised and no specific targeted therapies have been identified. Here, we describe the phenotype and genotype of aldehyde dehydrogenase high (ALDHhigh) and CD133+ve endometrial cancer stem cells and how adipocyte secreted mediators block the inhibitory effect of metformin on endometrial cancer stem cell activity. Ishikawa and Hec-1a cell lines were used to characterise ALDHhigh and CD133+ve endometrial cancer cells using flow cytometry, functional sphere assays and quantitative-Polymerase Chain Reaction. The comparative effect of metformin on endometrial cancer stem cell activity and bulk tumour cell proliferation was determined using an Aldefluor and cytotoxicity assay. The impact of adipocyte secreted mediators on metformin response was established using patient-derived conditioned media. ALDHhigh cells demonstrated greater endometrial cancer stem cell activity than CD133+ve cells and had increased expression of stem cell and epithelial-mesenchymal transition genes. Treatment with 0.5–1 mM metformin reduced the proportion and activity of both endometrial cancer stem cell populations (p ≤ 0.05), without affecting cell viability. This effect was, however, inhibited by exposure to patient-derived adipocyte conditioned media. These results indicate a selective and specific effect of metformin on endometrial cancer stem cell activity, which is blocked by adipocyte secreted mediators. Future studies of metformin as an adjuvant therapy in endometrial cancer should be adequately powered to investigate the influence of body mass on treatment response.
The Significant Reduction or Complete Eradication of Subcutaneous and Metastatic Lesions in a Pheochromocytoma Mouse Model after Immunotherapy Using Mannan-BAM, TLR Ligands, and Anti-CD40
Authors: Caisova Veronika , Li Liping , Gupta Garima , Jochmanova Ivana , Jha Abhishek , Uher Ondrej , Huynh Thanh-Truc , Miettinen Markku , Pang Ying , Abunimer Luma , Niu Gang , Chen Xiaoyuan , Ghayee Hans Kumar , Taïeb David , Zhuang Zhengping , Zenka Jan , Pacak Karel
Published: May 2019

Therapeutic options for metastatic pheochromocytoma/paraganglioma (PHEO/PGL) are limited. Here, we tested an immunotherapeutic approach based on intratumoral injections of mannan-BAM with toll-like receptor ligands into subcutaneous PHEO in a mouse model. This therapy elicited a strong innate immunity-mediated antitumor response and resulted in a significantly lower PHEO volume compared to the phosphate buffered saline (PBS)-treated group and in a significant improvement in mice survival. The cytotoxic effect of neutrophils, as innate immune cells predominantly infiltrating treated tumors, was verified in vitro. Moreover, the combination of mannan-BAM and toll-like receptor ligands with agonistic anti-CD40 was associated with increased mice survival. Subsequent tumor re-challenge also supported adaptive immunity activation, reflected primarily by long-term tumor-specific memory. These results were further verified in metastatic PHEO, where the intratumoral injections of mannan-BAM, toll-like receptor ligands, and anti-CD40 into subcutaneous tumors resulted in significantly less intense bioluminescence signals of liver metastatic lesions induced by tail vein injection compared to the PBS-treated group. Subsequent experiments focusing on the depletion of T cell subpopulations confirmed the crucial role of CD8+ T cells in inhibition of bioluminescence signal intensity of liver metastatic lesions. These data call for a new therapeutic approach in patients with metastatic PHEO/PGL using immunotherapy that initially activates innate immunity followed by an adaptive immune response.
Palliative Electrochemotherapy in Vulvar Carcinoma: Preliminary Results of the ELECHTRA (Electrochemotherapy Vulvar Cancer) Multicenter Study
Authors: Perrone Anna Myriam , Galuppi Andrea , Pirovano Cecilia , Borghese Giulia , Covarelli Piero , De Terlizzi Francesca , Ferioli Martina , Cara Silvia , Morganti Alessio Giuseppe , De Iaco Pierandrea
Published: May 2019

Vulvar cancer (VC) is a rare disease of which recurrence poses management problems due to patients’ advanced age and comorbidities, and to the localization of the disease. Palliative treatments, allowing local disease control in patients previously treated with multimodal therapies or with comorbidities, are lacking. In this study we tested electrochemotherapy (ECT) on recurrent VC refractory to standard therapies to assess the tumor response and to define the selection criteria for patient’s candidate to ECT. This is a multicenter observational study carried out in five Italian centers. Data about patients and tumor characteristics, treatment, toxicity, and clinical response were recorded. In all procedures, intravenous bleomycin was administered according to European Standard Operative Procedure ECT (ESOPE) guidelines. Sixty-one patients, with a median age 79 years (range: 39–85) and mainly affected by squamous cellular carcinoma (91.8%), were treated with ECT. No serious adverse events were reported. Patients were discharged after three days (median, range: 0–8 days). Two months after ECT, the clinical response rate was 83.6% and was not related to age, body mass index, International Federation of Gynecology and Obstetrics (FIGO) stage, number of treated nodules, or previous treatments. ECT is a safe procedure with a favorable cost-effectiveness ratio and should be considered as a treatment option for local disease control in patients unsuitable for standard therapies.
Chemoradiotherapy (Gemox Plus Helical Tomotherapy) for Unresectable Locally Advanced Pancreatic Cancer: A Phase II Study
Authors: Passardi Alessandro , Scarpi Emanuela , Neri Elisa , Parisi Elisabetta , Ghigi Giulia , Ercolani Giorgio , Gardini Andrea , La Barba Giuliano , Pagan Flavia , Casadei-Gardini Andrea , Valgiusti Martina , Ferroni Fabio , Frassineti Giovanni , Romeo Antonino
Published: May 2019

The aim of the study was to evaluate the safety and efficacy of a new chemo-radiotherapy regimen for patients with locally advanced pancreatic cancer (LAPC). Patients were treated as follows: gemcitabine 1000 mg/m2 on day 1, and oxaliplatin 100 mg/m2 on day 2, every two weeks (GEMOX regimen) for 4 cycles, 15 days off, hypofractionated radiotherapy (35 Gy in 7 fractions in 9 consecutive days), 15 days off, 4 additional cycles of GEMOX, restaging. From April 2011 to August 2016, a total of 42 patients with non resectable LAPC were enrolled. Median age was 67 years (range 41–75). Radiotherapy was well tolerated and the most frequently encountered adverse events were mild to moderate nausea and vomiting, abdominal pain and fatigue. In total, 9 patients underwent surgical laparotomy (5 radical pancreatic resection 1 thermoablation and 3 explorative laparotomy), 1 patient became operable but refused surgery. The overall resectability rate was 25%, while the R0 resection rate was 12.5%. At a median follow-up of 50 months, the median progression-free survival and overall survival were 9.3 (95% CI 6.2–14.9) and 15.8 (95% CI 8.2–23.4) months, respectively. The results demonstrate the feasibility of a new chemo-radiotherapy regimen as a potential treatment for unresectable LAPC.
Breast Cancer Tumor Stroma: Cellular Components, Phenotypic Heterogeneity, Intercellular Communication, Prognostic Implications and Therapeutic Opportunities
Authors: Eiro Noemi , Gonzalez Luis , Fraile María , Cid Sandra , Schneider Jose , Vizoso Francisco
Published: May 2019

Although the mechanisms underlying the genesis and progression of breast cancer are better understood than ever, it is still the most frequent malignant tumor in women and one of the leading causes of cancer death. Therefore, we need to establish new approaches that lead us to better understand the prognosis of this heterogeneous systemic disease and to propose new therapeutic strategies. Cancer is not only a malignant transformation of the epithelial cells merely based on their autonomous or acquired proliferative capacity. Today, data support the concept of cancer as an ecosystem based on a cellular sociology, with diverse components and complex interactions between them. Among the different cell types that make up the stroma, which have a relevant role in the dynamics of tumor/stromal cell interactions, the main ones are cancer associated fibroblasts, endothelial cells, immune cells and mesenchymal stromal cells. Several factors expressed by the stroma of breast carcinomas are associated with the development of metastasis, such as matrix metalloproteases, their tissular inhibitors or some of their regulators like integrins, cytokines or toll-like receptors. Based on the expression of these factors, two types of breast cancer stroma can be proposed with significantly different influence on the prognosis of patients. In addition, there is evidence about the existence of bi-directional signals between cancer cells and tumor stroma cells with prognostic implications, suggesting new therapeutic strategies in breast cancer.
Unusual Regularities of Propylene Carbonate Obtained by Propylene Oxide Carboxylation in the Presence of ZnBr2/Et4N+Br− System
Authors: Elman Alexander R. , Zharkov Sergei A. , Ovsyannikova Liudmila V.
Published: May 2019

The aim of the work was to study the unusual regularities of propylene carbonate prepared by carboxylation of propylene oxide in the presence of the catalytic system ZnBr2/Et4N+Br−. Using the kinetic method, a long induction period was detected, followed by the rapid formation of propylene carbonate in a quantitative yield, where the maximum turnover frequency (TOF) values reached 21,658 h−1. The regularities of the influence of the main process parameters on the induction period duration and the reaction rate were established. Based on the results obtained and considering the literature, assumptions about the mechanism of the process were proposed and ways for its further study were outlined.
Experimental Study for HIx Concentration by Electro-Electrodialysis (EED) Cells in the Water Splitting Sulfur-Iodine Thermochemical Cycle
Authors: Caputo Giampaolo , Balog Irena , Giaconia Alberto , Sau Salvatore , Pozio Alfonso
Published: May 2019

The efficiency of HI concentration/separation from a HIx solution, (mixture of HI/H2O/I2) represents a crucial factor in the sulfur-iodine thermochemical water splitting process for hydrogen production. In this paper, an experimental study on HI cathodic concentration in HIx solution using stacked electro-electrodialysis (EED) cells was carried out under the conditions of 1 atm and at three different temperature (25, 55 and 85 °C) and using a current density of 0.10 A/cm2. Results showed that an increase in HI concentration can be obtained under certain conditions. The apparent transport number (t+) in all the experiments was very close to 1, and the electro-osmosis coefficient (β) changed in a range of 1.08–1.16. The tests showed a detectable, though slow, increase in both the anodic iodine and cathodic hydriodic acid concentrations.
NICU Admissions for Meconium Aspiration Syndrome before and after a National Resuscitation Program Suctioning Guideline Change
Authors: Edwards Erika , Lakshminrusimha Satyan , Ehret Danielle , Horbar Jeffrey
Published: May 2019

The Textbook of Neonatal Resuscitation, seventh edition, does not suggest routine endotracheal suctioning for non-vigorous infants born through meconium-stained amniotic fluid. We compared 301,150 infants at ≥35 weeks’ gestational age inborn at 311 Vermont Oxford Network member centers in the United States (U.S.) and admitted to neonatal intensive care units (NICU) who were born before (2013 to 2015) and after (2017) the guideline change. Logistic regression models adjusting for clustering of infants within centers were used to calculate risk ratios. NICU admissions for infants with a diagnosis of meconium aspiration syndrome (MAS) decreased from 1.8% to 1.5% (risk ratio: 0.82; 95% confidence interval: 0.68, 0.97) and delivery room endotracheal suctioning in this group decreased from 57.0% to 28.9% (0.51; 0.41, 0.62). Treatment with conventional or high frequency ventilation, inhaled nitric oxide, or extracorporeal membrane oxygenation remained unchanged 42.3% vs. 40.3% (0.95; 0.80, 1.13) among infants with MAS and 9.1% vs. 8.2% (0.91; 0.87, 0.95) among infants without MAS. The use of surfactant among infants with MAS increased from 24.6% to 30% (1.22; 1.02, 1.48). Mortality (2.6 to 2.9%, 1.12; 0.74, 1.69) and moderate/severe hypoxic-ischemic encephalopathy (5.4 to 6.8%, 1.24; 0.91, 1.69) increased slightly in 2017. Subgroup analyses of infants with 1 min Apgar scores of ≤3 found similar results. While NICU admissions for MAS and tracheal suctioning decreased after the introduction of the new guideline with no subsequent increase in severe respiratory distress among infants with and without a MAS diagnosis, limitations in our study preclude inferring that the new guideline is safe or effective.