bluuebunny/crossref_metadata_2025 huggingface dataset:
Indicadores para medir la movilidad sostenible en espacios urbanos de la sierra ecuatoriana. Caso de estudio el cantón Azogues
Authors: León Andrade Mónica Piedad , Carriel Bustamante Viviana Veronica
Published: September 2021

Introducción. La movilidad sostenible se refiere a los desplazamientos origen-destino que existen en las ciudades, ya sea a través de transporte público, motorizados, vehículos privados, bicicletas, etc., brindando una calidad de vida óptima para la población y el medioambiente. Objetivo. El presente trabajo investigativo, tiene como objetivo general, encontrar algunos Indicadores para Medir la Movilidad Sostenible en Espacios Urbanos de la Sierra Ecuatoriana, utilizando como caso de estudio el Cantón Azogues. Metodología. Para lo cual, se identificaron diversas teorías sobre la movilidad sostenible en espacios urbanos y sus formas de medición a nivel internacional. Luego, diagnosticar la movilidad en el espacio urbano que comprende el Cantón Azogues, para finalmente diseñar los indicadores. En el desarrollo de la investigación se utiliza métodos teóricos y empíricos como: el análisis y la síntesis, el método deductivo e inductivo y la encuesta. El análisis y síntesis de utilizará para analizar a profundidad el objeto de estudio. El método deductivo e inductivo nos ayudará a comprender las generalidades teóricas en cuanto a la movilidad urbana sostenible y sus formas de medición. Y por último la encuesta ayudará como un procedimiento en la recopilación de datos mediante un cuestionario previamente diseñado. Resultados. Se evidencia que la mayoría de personas se transporta a otros lugares por motivos de trabajo (61.7%) y solo un mínimo porcentaje (2%) permanece en casa sin movilizarse. Conclusión. La aplicación de estos indicadores en el caso del Cantón Azogues, es el primer paso para la evaluación de los diferentes ámbitos de la sostenibilidad en temas de movilidad, con lo que se pretende la implementación de nuevas políticas que mejoren los aspectos sociales, económicos y ambientales de la ciudad.
Cost per responder for risankizumab vs secukinumab in patients with moderate-to-severe plaque psoriasis in Italy
Authors: Gisondi Paolo , Loconsole Francesco , Raimondo Paola , Ravasio Roberto
Published: September 2021

Purpose: The objective of this analysis was to compare the cost per responder between risankizumab and secukinumab among patients with moderate-to-severe plaque psoriasis in Italy.
Methods: The clinical efficacy was assessed based on IMMerge study of published efficacy data as measured by Psoriasis Area and Severity Index response (PASI 90 and PASI 100) for risankizumab and secukinumab. The treatment cost was based on the number of administrations dispensed in the first (induction plus maintenance period) and the second (maintenance period only) year of treatment and the ex-factory price of each treatment. The cost per responder was adopted as a cost-effectiveness indicator.
Results: Independently of the PASI response (PASI 90 and PASI 100) used and the year of treatment considered, the cost per responder was consistently lower for risankizumab compared to secukinumab in all clinical measures. For example, considering the first-year costs and PASI 100, the cost per responder for risankizumab was € 24,506.83 compared to € 38,000.00 for secukinumab. The differences in the cost per responder between risankizumab and secukinumab increased when higher PASI response levels were considered.
Conclusion: This economic evaluation suggested that the cost per responder is consistently lower for risankizumab compared to secukinumab from the perspective of the Italian National Health Service in the treatment of moderate-to-severe plaque psoriasis.
New data on the age of the Middle Palaeolithic site of Proniatyn (Podolian Upland)
Authors: Bogucki Andriy , Tomeniuk Olena , Sytnyk Oleksandr , Koropetskyi Ruslan
Published: September 2021

The Middle Palaeolithic site Proniatyn is geomorphologically located on the near-watershed slope of the right bank of the Seret River. The history of its archaeological research began in 1977. During numerous expedition seasons of works conducted with using of methods of natural sciences and archaeology (until 2015), rich flint material was found on the site, which was located in the deposits of the over-Horokhiv deluvial solifluction stratum, i.e. not in situ, but was moved down the slope. The upper chronological limit of the cultural horizon was determined as 85±7 ka (according to V. Shovkoplias) by TL-dating of the Upper Pleistocene loess, which overlaps the over-Horokhiv deluvial solifluction stratum.
In 2015, the Proniatyn site became the subject of scientific excursion of the international loess seminar «Loesses and Palaeolithic of Podillia». To clarify the age of the site, survey pit 5, located directly next to the main excavation, in the southern part of the site was expanded and deepened. The main goal of the work was to search for artifacts in the Horokhiv fossil pedocomplex (MIS 5), which is only slightly disturbed by deluvial-solifluctional processes. Two artifacts were found in the eluvial horizon of this complex, the third one was found in its humus horizon.
Detailed analysis of the finds shows that the additional flint artifacts discovered in 2015 do not contradict the conclusion that technical, morphological and typological features of these three flints are completely identical to several thousand previously excavated flints from this site and represent the flake-blade Levallois industry. In general, all discovered artifacts from Proniatyn form a single monocultural complex of the site.
Based on research conducted in 2015 is clearly established that the age of Proniatyn cultural horizon does not correspond to the age of deluvial-solifluctional strata, as previously thought, but is older than it. It is associated with the eluvial horizon of the Horokhiv fossil soil complex, the age of which is estimated at 112,0±11,2 ka and 106,7±11 ka according to TL-dating (the Palaeolithic site Yezupil I), 110±18 ka according to TL-dating and 102±16 ka according to OSL-dating (Palaeolithic site Mariampil I).
Key words: Middle Palaeolithic, artifact, Mousterian, loess-palaeosol sequence, deluvial-solifluctional processes, Podillia.
Surgical Outcomes of Nonadjustable Modified Harada-Ito Surgery
Authors: Yoon Yi Sang , Kim Ungsoo Samuel
Published: September 2021

Purpose: This study aimed to investigate the surgical outcomes of nonadjustable Harada-Ito surgery under general anesthesia.Methods: Twenty-two patients who underwent nonadjustable modified Harada-Ito surgery under general anesthesia were reviewed retrospectively. Among them, 21 out of the 22 patients who were followed up for 6 months after surgery were included in this study. Subjective cyclotorsion (double Maddox rod test) and objective cyclotorsions (fundus photography) were measured. Success of the surgery was defined as follows: success (the patients do not acknowledge diplopia at any direction), partial (the patients feel diplopia at a specific direction, but they do not feel discomfort in routine life), and fail (the patients feel diplopia in primary gaze, hence requiring a thorough investigation).Results: The mean age of the patients (18 male and 3 female) was 56.5 years (range, 40–77 years). Based on the alternate prism cover test, the patients had 4.2 ± 3.0 prism diopters of vertical deviation. The corrected amounts of cyclotorsion based on the double Maddox rod test and fundus photography were 14.8° ± 7.5° and 9.8° ± 7.9°, respectively, and were significantly different between the two methods (p = 0.006). After the surgery, 20 out of the 21 patients (95.2%) completely recovered from diplopia in the primary gaze. However, among the 20 patients, seven complained of diplopia in the secondary gaze (down gaze, four patients; head tilt gaze, three patients). The success group had a smaller preoperative subjective excyclotorsion than the partial and fail groups (12.6° ± 2.5° and 21.0° ± 8.9°, respectively; p = 0.046).Conclusions: Nonadjustable modified Harada-Ito surgery under general anesthesia has favorable success rate, and preoperative subjective excyclotorsion can be a prognostic factor in patients with bilateral superior oblique palsy.
PEMBERDAYAAN PETANI RUMPUT LAUT DI KAMPUNG SARAWANDORI DISTRIK KOSIWO KABUPATEN KEPULAUAN YAPEN
Authors: Rifa'i Mohammad , Kirihio Sheryl Viola A.
Published: September 2021

The potential for marine products in the Yapen Islands is very abundant, including seaweed. However, it should be noted that coastal communities who work as seaweed farmers with all their limitations also face several problems, including limited knowledge and skills in seaweed cultivation, use of simple tools (raft method), traditional/hereditary cultivation methods, and the marketing of crops, whose reach is still limited. For this reason, the Regional Government through the Marine and Fisheries Service provides support and assistance in the context of empowering seaweed farmers. The purpose of writing this is to find out the process of empowering seaweed farmers in Sarawandori Village. Else, to explore the obstacles and supporting factors of the empowerment. This research used a qualitative research method with a descriptive approach. The results showed that the empowerment of seaweed farmers had been running even though the results were not optimal. For this reason, the government through the Yapen Islands Regency Maritime Affairs and Fisheries Office seeks to help farmers in the seaweed cultivation process, and facilitate farmers to be able to use more sophisticated technology and expand the marketing reach of seaweed and its processed products from Sarawandori Village to outside the Yapen Islands.

Keywords: Empowerment, Seaweed, Farmer, Yapen Regency
PEMBERDAYAAN MASYARAKAT PENGELOLA OBYEK WISATA PANTAI HARLEM DI KAMPUNG TABLASUPA OLEH DINAS KEBUDAYAAN DAN PARIWISATA KABUPATEN JAYAPURA
Authors: Mulyana Mulyana , Siby Evan Stanley
Published: September 2021

Harlem Beach is one of the tourist objects in Jayapura Regency which has the potential to improve the welfare of the people of Tablasupa Village. This study aims to determine an overview of the community empowerment efforts of Harlem Beach managers based on their potential. This research uses descriptive qualitative method with an inductive approach. The data collection techniques used by the author are unstructured interviews using outlines of the problem, observation, documentation and triangulation of data sources. Data analysis techniques using data reduction, data presentation, and drawing conclusions. An interesting finding in this conclusion is that the empowerment of the community managing Harlem Beach tourism objects by the Jayapura Regency Culture and Tourism Office uses the AGIL concept by building facilities, providing skills training and carrying out promotions but is still constrained by issues of customary rights, limited facilities and infrastructure. The conclusion of this study is that the empowerment efforts carried out based on the AGIL concept are considered to be not optimal, because they are hampered by several factors such as lack of facilities, poor infrastructure, unclear customary rights, lack of capital, the absence of BUMKAM and a lack of community mindset.

Keywords: empowerment, community, beach tourism
PENGEMBANGAN KAWASAN AGROWISATA KEBUN BELIMBING DI KECAMATAN TAWANGHARJO, KABUPATEN GROBOGAN, PROVINSI JAWA TENGAH
Authors: Visa Sandy Rhey Pasha , Hamid Hendrawati , Fadhilah Hasna Azmi
Published: September 2021

Tawangharjo is a sub-district that is going to be developed as a new destination of Agrotourism. This agrotourism is classified as a new type of tourism in Grobogan Regency. This study aims to determine and analyze how the development of agrotourism in Tawangharjo District, as well as to explain the inhibiting factors and efforts made by the government and local agencies in developing the agrotourism area. This study used descriptive qualitative method with an inductive approach, combined with observation, interviews, and documentation. Further, the authors analysed the data by creating a data map, exploring data presentation, comparing all data, then drawing conclusion. The results show that the indicators for the development of the Starfruit Garden Agrotourism Area, Tawangharjo Sub-district, were still not met, Amenities and Ancillary become the main problems because physical development required time and budget, while facilities were the main support for agrotourism activities. In addition, the Covid-19 pandemic has further exacerbated the situation by refocusing the budget and significantly reducing the number of tourists. The quality of human resources needs to be improved, including the managers’ capacity and the community's ability to diversify, promote, and multiply the products. As a suggestion, the Grobogan Regency government should further optimize the tourism program and policies, in order to increase production capacity and develop agrotourism facilities.

Keyword: Development, Tourism, Agrotourism
EFFECTIVENESS OF BUNDO PEDULI JENTIK PROGRAM IN CONTROLLING THE DENGUE HEMORRHAGIC FEVER
Authors: Anggraini Wike , Arwanto Arwanto , Danda Saskia Pratiwi
Published: September 2021

Abstract

Dengue Hemorrhagic Fever(DHF) was the deadliest disease in Indonesia with the highest number of cases in 2016. This study aims to determine the effectiveness of Bundo Peduli Jentik program, one of the Health Department of Padang City Government programs, in controlling DHF, especially in Lubuk Kilangan Sub-district. This is a descriptive qualitative research with an inductive approach. Data and information collection were done by observation, interviews and documentation. The theory used is the theory of effectiveness proposed by Budiani that measures effectiveness comprising the accuracy of program targets, program socialization, program objectives and program monitoring. The result showed that the Bundo Peduli Jentik program has been categorized as effective based on the theory used. This is proven by the DHF cases continue to decline every year and there were no number of deaths due to DHF since 2017 in Lubuk Kilangan, Padang City.

 

Keywords: Dengue Hemorrhagic Fever, Effectiveness, Government Program

Abstrak

Demam Berdarah Dengue (DBD) pernah menjadi penyakit paling mematikan di Indonesia dengan jumlah kasus terbanyak di tahun 2016. Penelitian ini bertujuan untuk mengetahui efektivitas program Bundo Peduli Jentik, salah satu program Dinas Kesehatan Pemerintah Kota Padang, dalam pengendalian DBD terutama di Kecamatan Lubuk Kilangan. Metode penelitian dalam penelitian ini adalah metode kualitatif deskriptif dengan pendekatan induktif. Pengumpulan data dan informasi dilakukan dengan cara observasi, wawancara dan dokumentasi. Teori yang digunakan dalam penelitian ini adalah teori efektivitas yang dikemukakan oleh Budiani yang mengukur efektivitas menggunakan variabel-variabel, diantaranya ketepatan sasaran program, sosialisasi program, tujuan program dan pemantauan program. Hasil penelitian menunjukkan bahwa program Bundo Peduli Jentik dapat dikategorikan efektif berdasarkan teori yang digunakan. Hal ini dibuktikan dengan kasus DBD yang terus menurun setiap tahunnya bahkan tidak ada lagi kasus kematian karena DBD sejak tahun 2017 di Kecamatan Lubuk Kilangan, Kota Padang.

 

Kata Kunci: Demam Berdarah Dengue, Efektivitas, Program Pemerintah
DEWAN PERWAKILAN DAERAH DAN AKTUALISASI HUBUNGAN PUSAT-DAERAH
Authors: Kuddus Baharuddin Thahir
Published: September 2021

Distribusi kekuasaan pada sebuah Negara dapat dilihat dari dua hal, yaitu distribusi kekuasaan secara vertical dan distribusi kekuasaan secara vertical. Distribusi kekuasaan secara vertical dapat dilihat dalam pelaksanaan desentralisasi melalui otonomi daerah sementara distribusi kekuasaan dapat dilihat pada eksistensi dan hubungan antara lembaga-lembaga Negara. Kebijakan desentralisasi didasarkan pada kenyataan bahwa keadaan geografis dan demografis Indonesia (conditiosine qua non). Dalam pelaksanaan desentralisasi, hubungan pusat dan daerah seringkali melahirkan konflik. Hal itu berkenaan dengan derajat otonomi daerah dan pada saat yang sama kadar keterlibatan pusat dalam pelaksanaan fungsi pemerintahan di daerah. Hal itu berarti terdapat dua kepentingan yang harus dipertimbangkan supaya tatanan sistem pemerintahan daerah dapat berjalan dengan optimal dan memenuhi amanat konstitusi.

Sementara itu dalam sistem ketatanegaraan Indonesia, Dewan Perwakilan Daerah ditempatkan sebagai salah satu unsur lembaga legislatif, disamping lembaga Dewan Perwakilan Rakyat.  DPD mestinya menjadi penting antara lain disebabkan posisinya yang sangat strategis dalam melakukan pengawasan terhadap pelaksanaan peraturan perundang-undangan dan pelaksanaan kebijakan pemerintah. Dalam konteks distribusi kekuasaan secara horizontal itu pula maka Dewan Perwakilan Daerah diadakan untuk  check and balances. DPD menjadi instrument kelembagaan yang semakin menghadirkan aspirasi daerah di level pusat dan menjadikan hubungan pusat dan daerah semakin erat dan bersinergi dalam menjalankan roda pemerintahan.
MEMAHAMI KEBIJAKAN PENGEMBANGAN AGROWISATA DI KABUPATEN CIAMIS: DINAMIKA SUMBER DAYA ALAM LOKAL DAN KEBUDAYAAN
Authors: Nurwanda Asep , Badriah Elis , Nursetiawan Irfan
Published: September 2021

This study aims to determine the condition of agro-tourism based on local natural resources and local wisdom based on the culture of Ciamis district. The effort to develop agro-tourism based on local culture is a form of effort to improve the quality and quantity of infrastructure and improve the quality of resources as an effort to develop tourism. with the existence of this agro-tourism concept, it is not only a business or business in the service sector that markets services towards consumer fulfillment of cool air, and beautiful scenery and environment, but is also able to take a role as a place for promotion of agricultural products, as a place of education for residents , gives hope to the potential to develop products from agribusiness and can become a new growth area. Therefore, agro-tourism is able to become a source of regional economy. Research methods use a qualitative descriptive approach, so that the application of activities in developing agro-tourism based on local natural resources and based on cultural wisdom, there is still a lack of assistance in human resource development and training and lack of communication between the government and community groups. culture and business groups.
DETERMINAN DAN KEBIJAKAN PENANGANAN STUNTING DI INDONESIA
Authors: Zulkarnaen Zulkarnaen , Soesilo Nining Indroyono
Published: September 2021

Stunting merupakan suatu keadaan pendek badan (kerdil) yang terjadi pada anak jika dibandingkan dengan kelompok umur. Anak mengalami stunting jika tinggi badan yang dimiliki minus dua (pendek) atau minus tiga (sangat pendek) dari standar deviasi yang ditentukan WHO. Penelitian ini bertujuan untuk menguji pengaruh DAK bidang kesehatan terhadap penurunan stunting di Indonesia dengan membangun model stunting berdasarkan pendekatan literature yang dilakukan. Hasil penelitian menunjukkan bahwa DAK bidang kesehatan tidak berdampak terhadap peningkatan banyaknya ibu hamil yang mengonsumsi TTD. Sementara, banyaknya ibu hamil yang mengonsumsi TTD berdampak terhadap penurunan stunting secara signifikan. Adapun keterbatasan penelitian ini adalah sebagai berikut: (i) Faktor-faktor penyebab stunting dari aspek immediate Causes dan underlying causes seperti bayi lahir premature, berat badan lahir rendah, penyakit infeksi, durasi ASI, usia ibu, interval kehamilan, vaksinisasi bayi dan aspek layanan kesehatan tidak dikaji sepenuhnya karena keterbatasan data dan fokus studi utamanya pada aspek sosioekonomi. (ii) Faktor-faktor yang dapat mengintervensi stunting dari sisi lain kebijakan DAK bidang Kesehatan belum sepenuhnya diteliti seperti aspek JAMPERSAL, perbaikan infrastruktur puskesmas dan posyandu, dan (iii) Data-data yang mewakili variabel seperti pendapatan masih sangat makro dan tidak mengestimasi pendapatan individu secara menyeluruh.
INTERNALISASI AGILE ORGANIZATIONS DALAM PENYEDERHANAAN ESELONISASI UNTUK MENINGKATKAN KINERJA PEMERINTAHAN DI INSTITUT PEMERINTAHAN DALAM NEGERI KEMENTERIAN DALAM NEGERI
Authors: Pitono Andi , Kartiwi Kartiwi , Baidhowah Adfin Rochmad
Published: September 2021

growing in Indonesia. Strategic steps for the possibility of internalizing the values ​​of the five trademarks of agile organizations in downsizing bureaucracy to improve government performance at the Institut Pemerintahan Dalam Negeri can be carried out, through mapping the Institut Pemerintahan Dalam Negeri organizational structure containing echelon 3 and echelon 4 positions, changing the organizational structure of IPDN which is simplified, implementing economic incentives and job appraisal requirements, implementing one data, conducting job analysis, workload analysis, and job mapping, implementing flexible financial and human resource management, and preparing for a transition period.
ANALISIS IMPLEMENTASI KEBIJAKAN PEMBENTUKAN DAERAH OTONOM BARU (DOB) PROVINSI PAPUA TENGAH
Authors: Cahyadi M Fikri , Kurniawan Teguh
Published: September 2021

DOB dapat meningkatkan pelayanan publik dan mewujudkan efektivitas penyelenggaraan pemerintahan di daerah. Parameter yang digunakan melalui Rasio SDM Aparatur, Ekonomi, Pendidikan, Kesehatan, Kependudukan dan Fiskal Daerah menjadi tolak ukur bahwa pembentukan DOB dalam meningkatkan pelayanan publik sudah dapat direalisasikan. Penulisan ini menggunakan pendekatan kualitatif dengan metode pengumpulan data studi literatur (literatur reviu) melalui dokumentasi terkait dengan penelitian dalam bentuk Kajian Strategis, Tesis dan Disertasi tentang Pembentukan DOB, serta melalui peraturan perundang-undangan yang berkaitan dengan penelitian. Hasil penulisan menunjukkan bahwa sinergitas dalam pembinaan, pendampingan serta upaya peningkatan pelayanan kepada masyarakat dalam penyelenggaraan DOB menuju daerah otonom maju dan mandiri dapat diukur melalui parameter yang untuk mencapai sasaran yang ditetapkan dalam pelayanan kepada masyarakat.

Kata Kunci: Daerah Otonom, DOB, Pelayanan Publik, Pemerintahan Daerah
MENINGKATKAN KETERAMPILAN MENGOPERASIKAN PERALATAN EKSTRAKSI MELALUI MODEL PEMBELAJARAN POE (PREDICT, OBSERVE, EXPLAIN)
Authors: Siti Nurjanna
Published: September 2021

This study aims to enhance the skills of students to operate extraction equipment. This is a two-cycle Classroom Action Search. The focus of the research was students in class XI E, which consisted of 15 people. The data-gathering technique uses non-test instrument. The data analysis technique used qualitative analysis. The results showed an increase in the skills of the extraction equipment. Completeness of learning cycle I was 66.67% and increased to 93.33%. Meanwhile, the average score of students' skills increased from 74.63 in the first cycle to 80.39 in the second cycle, with value of Asymp.Sig.(2-tailed) 0.005 < 0.05, which means that there is a significant difference between the average class value in cycle I and the average class value in cycle II.  Ignorance that the POE learning model can improve skills to operate extraction equipment.

Penelitian ini bertujuan untuk meningkatkan keterampilan mengoperasikan peralatan ekstraksi. Penelitian ini merupakan Penelitian Tindakan Kelas dengan 2 siklus. Obyek penelitian adalah siswa kelas XI E yang berjumlah 15 orang. Teknik pengumpulan data berupa instrumen non tes. Teknik analisis data menggunakan analisis kualitatif. Hasil penelitian menunjukkan terjadi peningkatan keterampilan mengoperasikan peralatan ekstraksi. Ketuntasan belajar siklus I sebesar 66,67% meningkat menjadi 93,33%. Sedangkan rata-rata nilai keterampilan siswa meningkat dari 74,63 pada siklus I menjadi 80,39 pada siklus II, dengan nilai Asymp.Sig.(2-tailed) 0,005 < 0,05, berarti terdapat perbedaan yang signifikan antara rata-rata nilai siklus I dengan rata-rata nilai siklus II. Disimpulkan bahwa penerapan model pembelajaran POE dapat meningkatkan keterampilan mengoperasikan peralatan ekstraksi.
Silica-Based Nanoframeworks Involved Hepatocellular Carcinoma Theranostic
Authors: Liu Yunxi , Chen Yue , Fei Weidong , Zheng Caihong , Zheng Yongquan , Tang Miao , Qian Ying , Zhang Xiao , Zhao Mengdan , Zhang Meng , Wang Fengmei
Published: September 2021

Silica-based nanoframeworks have been extensively studied for diagnosing and treating hepatocellular carcinoma (HCC). Several reviews have summarized the advantages and disadvantages of these nanoframeworks and their use as drug-delivery carriers. Encouragingly, these nanoframeworks, especially those with metal elements or small molecular drugs doping into the skeleton structure or modifying onto the surface of nanoparticles, could be multifunctional components participating in HCC diagnosis and treatment rather than functioning only as drug-delivery carriers. Therefore, in this work, we described the research progress of silica-based nanoframeworks involved in HCC diagnosis (plasma biomarker detection, magnetic resonance imaging, positron emission tomography, photoacoustic imaging, fluorescent imaging, ultrasonography, etc.) and treatment (chemotherapy, ferroptotic therapy, radiotherapy, phototherapy, sonodynamic therapy, immunotherapy, etc.) to clarify their roles in HCC theranostics. Further, the future expectations and challenges associated with silica-based nanoframeworks were highlighted. We believe that this review will provide a comprehensive understanding for researchers to design novel, functional silica-based nanoframeworks that can effectively overcome HCC.
Computed Tomography Coronary Angiography and Computational Fluid Dynamics Based Fractional Flow Reserve Before and After Percutaneous Coronary Intervention
Authors: Chandola Gaurav , Zhang Jun-Mei , Tan Ru-San , Chai Ping , Teo Lynette , Allen John C. , Low Ris , Huang Weimin , Leng Shuang , Fam Jiang Ming , Chin Chee Yang , Kassab Ghassan S. , Low Adrian Fatt Hoe , Tan Swee Yaw , Chua Terrance , Lim Soo Teik , Zhong Liang
Published: September 2021

Invasive fractional flow reserve (FFR) is recommended to guide stent deployment. We previously introduced a non-invasive FFR calculation (FFRB) based on computed tomography coronary angiography (CTCA) with reduced-order computational fluid dynamics (CFD) and resistance boundary conditions. Current study aimed to assess the feasibility and accuracy of FFRB for predicting coronary hemodynamics before and after stenting, with invasive FFR as the reference. Twenty-five patients who had undergone CTCA were prospectively enrolled before invasive coronary angiography (ICA) and FFR-guided percutaneous coronary intervention (PCI) on 30 coronary vessels. Using reduced-order CFD with novel boundary conditions on three-dimensional (3D) patient-specific anatomic models reconstructed from CTCA, we calculated FFRB before and after virtual stenting. The latter simulated PCI by clipping stenotic segments from the 3D coronary models and replacing them with segments to mimic the deployed coronary stents. Pre- and post-virtual stenting FFRB were compared with FFR measured pre- and post-PCI by investigators blinded to FFRB results. Among 30 coronary lesions, pre-stenting FFRB (mean 0.69 ± 0.12) and FFR (mean 0.67 ± 0.13) exhibited good correlation (r = 0.86, p < 0.001) and agreement [mean difference 0.024, 95% limits of agreement (LoA): −0.11, 0.15]. Similarly, post-stenting FFRB (mean 0.84 ± 0.10) and FFR (mean 0.86 ± 0.08) exhibited fair correlation (r = 0.50, p < 0.001) and good agreement (mean difference 0.024, 95% LoA: −0.20, 0.16). The accuracy of FFRB for identifying post-stenting ischemic lesions (FFR ≤ 0.8) (residual ischemia) was 87% (sensitivity 80%, specificity 88%). Our novel FFRB, based on CTCA with reduced-order CFD and resistance boundary conditions, accurately predicts the hemodynamic effects of stenting which may serve as a tool in PCI planning.
A Three-Dimensional Imaging Method for the Quantification and Localization of Dynamic Cell Tracking Posttransplantation
Authors: Lu Fengfeng , Pan Xin , Zhang Wencheng , Su Xin , Gu Yuying , Qiu Hua , Shen Shengwei , Liu Changcheng , Liu Wei , Wang Xicheng , Zhan Zhenzhen , Liu Zhongmin , He Zhiying
Published: September 2021

Cell transplantation has been proposed as a promising therapeutic strategy for curing the diseases requiring tissue repairing and functional restoration. A preclinical method to systematically evaluate the fates of donor cells in recipients, spatially and temporally, is demanded for judging therapeutic potentials for the particularly designed cell transplantation. Yet, the dynamic cell tracking methodology for tracing transplanted cells in vivo is still at its early phase. Here, we created a practical protocol for dynamically tracking cell via a three-dimensional (3D) technique which enabled us to localize, quantify, and overall evaluate the transplanted hepatocytes within a liver failure mouse model. First, the capacity of 3D bioluminescence imaging for quantifying transplanted hepatocytes was defined. Images obtained from the 3D bioluminescence imaging module were then combined with the CT scanner to reconstruct structure images of host mice. With those reconstructed images, precise locations of transplanted hepatocytes in the liver of the recipient were dynamically monitored. Immunohistochemistry staining of transplanted cells, and the serology assay of liver panel of the host mice were applied to verify the successful engraftment of donor cells in the host livers. Our protocol was practical for evaluating the engraftment efficiency of donor cells at their preclinical phases, which is also applicable as a referable standard for studying the fates of other transplanted cells, such as stem cell-derived cell types, during preclinical studies with cell transplantation therapy.
Deregulated Rac1 Activity in Neural Crest Controls Cell Proliferation, Migration and Differentiation During Midbrain Development
Authors: Gahankari Apurva , Dong Chunmin , Bartoletti Garrett , Galazo Maria , He Fenglei
Published: September 2021

Mutations in RAC1 allele are implicated in multiple brain tumors, indicating a rigorous control of Rac1 activity is required for neural tissue normal development and homeostasis. To understand how elevated Rac1 activity affects neural crest cells (NCCs) development, we have generated Rac1CA;Wnt1-Cre2 mice, in which a constitutively active Rac1G12V mutant is expressed specifically in NCCs derivatives. Our results revealed that augmented Rac1 activity leads to enlarged midbrain and altered cell density, accompanied by increased NCCs proliferation rate and misrouted cell migration. Interestingly, our experimental data also showed that elevated Rac1 activity in NCCs disrupts regionalization of dopaminergic neuron progenitors in the ventral midbrain and impairs their differentiation. These findings shed light on the mechanisms of RAC1 mutation correlated brain tumor at the cellular and molecular level.
Identification and Validation of a Nine-Gene Amino Acid Metabolism-Related Risk Signature in HCC
Authors: Zhao Yajuan , Zhang Junli , Wang Shuhan , Jiang Qianqian , Xu Keshu
Published: September 2021

Background: Hepatocellular carcinoma (HCC) is the world’s second most deadly cancer, and metabolic reprogramming is its distinguishing feature. Among metabolite profiling, variation in amino acid metabolism supports tumor proliferation and metastasis to the most extent, yet a systematic study on the role of amino acid metabolism-related genes in HCC is still lacking. An effective amino acid metabolism-related prediction signature is urgently needed to assess the prognosis of HCC patients for individualized treatment.

Materials and Methods: RNA-seq data of HCC from the TCGA-LIHC and GSE14520 (GPL3921) datasets were defined as the training set and validation set, respectively. Amino acid metabolic genes were extracted from the Molecular Signature Database. Univariate Cox and LASSO regression analyses were performed to build a predictive risk signature. K-M curves, ROC curves, and univariate and multivariate Cox regression were conducted to evaluate the predictive value of this risk signature. Functional enrichment was analyzed by GSEA and CIBERSORTx software.

Results: A nine-gene amino acid metabolism-related risk signature including B3GAT3, B4GALT2, CYB5R3, GNPDA1, GOT2, HEXB, HMGCS2, PLOD2, and SEPHS1 was constructed to predict the overall survival (OS) of HCC patients. Patients were separated into high-risk and low-risk groups based on risk scores and low-risk patients had lower risk scores and longer survival time. Univariate and multivariate Cox regression verified that this signature was an independent risk factor for HCC. ROC curves showed that this risk signature can effectively predict the 1-, 2-, 3- and 5-year survival times of patients with HCC. Additionally, prognostic nomograms were established based on the training set and validation set. These genes were closely correlated with the immune regulation.

Conclusion: Our study identified a nine-gene amino acid metabolism-related risk signature and built predictive nomograms for OS in HCC. These findings will help us to personalize the treatment of liver cancer patients.
Early Leukocyte Responses in Ex-Vivo Models of Healing and Non-Healing Human Leishmania (Viannia) panamensis Infections
Authors: Gomez Maria Adelaida , Belew Ashton Trey , Navas Adriana , Rosales-Chilama Mariana , Murillo Julieth , Dillon Laura A. L. , Alexander Theresa A. , Martinez-Valencia Alvaro , El-Sayed Najib M.
Published: September 2021

Early host-pathogen interactions drive the host response and shape the outcome of natural infections caused by intracellular microorganisms. These interactions involve a number of immune and non-immune cells and tissues, along with an assortment of host and pathogen-derived molecules. Our current knowledge has been predominantly derived from research on the relationships between the pathogens and the invaded host cell(s), limiting our understanding of how microbes elicit and modulate immunological responses at the organismal level. In this study, we explored the early host determinants of healing and non-healing responses in human cutaneous leishmaniasis (CL) caused byLeishmania (Viannia) panamensis. We performed a comparative transcriptomic profiling of peripheral blood mononuclear cells from healthy donors (PBMCs, n=3) exposed to promastigotes isolated from patients with chronic (CHR, n=3) or self-healing (SH, n=3) CL, and compared these to human macrophage responses. Transcriptomes ofL. V. panamensis-infected PBMCs showed enrichment of functional gene categories derived from innate as well as adaptive immune cells signatures, demonstrating thatLeishmaniamodulates adaptive immune cell functions as early as after 24h post interaction with PBMCs from previously unexposed healthy individuals. Among differentially expressed PBMC genes, four broad categories were commonly modulated by SH and CHR strains: cell cycle/proliferation/differentiation, metabolism of macromolecules, immune signaling and vesicle trafficking/transport; the first two were predominantly downregulated, and the latter upregulated in SH and CHR as compared to uninfected samples. Type I IFN signaling genes were uniquely up-regulated in PBMCs infected with CHR strains, while genes involved in the immunological synapse were uniquely downregulated in SH infections. Similarly, pro-inflammatory response genes were upregulated in isolated macrophages infected with CHR strains. Our data demonstrate that early responses duringLeishmaniainfection extend beyond innate cell and/or phagocytic host cell functions, opening new frontiers in our understanding of the triggers and drivers of human CL.
Azole Use in Agriculture, Horticulture, and Wood Preservation – Is It Indispensable?
Authors: Jørgensen Lise Nistrup , Heick Thies Marten
Published: September 2021

Plant pathogens cause significant damage to plant products, compromising both quantities and quality. Even though many elements of agricultural practices are an integral part of reducing disease attacks, modern agriculture is still highly reliant on fungicides to guarantee high yields and product quality. The azoles, 14-alpha demethylase inhibitors, have been the fungicide class used most widely to control fungal plant diseases for more than four decades. More than 25 different azoles have been developed for the control of plant diseases in crops and the group has a world market value share of 20-25%. Azoles have proven to provide long-lasting control of many target plant pathogens and are categorized to have moderate risk for developing fungicide resistance. Field performances against many fungal pathogens have correspondingly been stable or only moderately reduced over time. Hence azoles are still, to date, considered the backbone in many control strategies and widely used as solo fungicides or as mixing partners with other fungicide groups, broadening the control spectrum as well as minimizing the overall risk of resistance development. This review describes the historic perspective of azoles, their market shares and importance for production of major crops like cereals, rice, oilseed rape, sugar beet, banana, citrus, and soybeans. In addition, information regarding use in amenity grass, in the wood preservation industry and as plant growth regulators are described. At the end of the review azoles are discussed in a wider context including future threats following stricter requirements for registration and potential impact on human health.
Recall and Understanding of Discharge Information in Observation Ward Patients: An Explorative Observational Study
Authors: Østen Kjersti , Menichetti Julia , Nordfalk Jenny M. , Ofstad Eirik H.
Published: September 2021

Effective communication is essential for understanding and recall of hospital discharge information. This study aimed to explore discharge information, patient recall and patient involvement in discharge encounters. We conducted an explorative observational study at a secondary care level, observational ward. Patients discharged to their home were asked to participate. 34 patients were assessed for eligibility, of which 13 were included in the analysis. Multiple sources of data were collected: videotapes of discharge encounters, questionnaires to patients and physicians, and semi-structured interviews with patients 2 weeks after discharge. All patients were satisfied with the information received. Five of the eight patients discharged with more than one change in medication had only partial or no recall of these changes. In seven of the 13 encounters the patients and physicians did not agree on the main message most important information item. The patients were to a small extent involved in decision-making. Our findings highlight the gaps in the information exchange at discharge encounters and the resulting poor information recall among patients. Patients do not seem aware of these gaps. Greater provider awareness of patient involvement in the encounter and inclusion of the patient’s perspective may improve communication, and consequently understanding and recall.
Central Systolic Blood Pressure Is Associated With Early Vascular Damage in Children and Adolescents With Type 1 Diabetes
Authors: Tagetti Angela , Piona Claudia A. , Marcon Denise , Giontella Alice , Branz Lorella , Bortolotti Stefano , Morandi Anita , Maffeis Claudio , Fava Cristiano
Published: September 2021

Objective of the study: This study aimed to test the effect of multiple cardiovascular risk factors on subclinical indices of atherosclerosis in children and adolescents with type 1 diabetes (T1D).

Methods: Carotid intima-media thickness (cIMT), carotid distensibility coefficient (cDC), and carotid–femoral pulse wave velocity (PWV) were measured in children and adolescents with T1D, in a follow-up at the outpatient clinics of Verona. Blood pressure (BP; both central and peripheral), metabolic and other cardiovascular risk factors were evaluated in multivariate linear regressions to assess the association with the measured indices of subclinical vascular damage.

Results: One hundred and twenty-six children and adolescents were included. cIMT was above the 95th percentile for age and height in 60.8% of the population, whereas 26% of the sample had cDC impairment (less than the 5th percentile) and 4.8% had an elevated PWV. Independent determinants of cIMT according to the regression models were only gender type of glucose monitoring and central systolic BP (cSBP). PWV was associated with age, sex, heart rate, and cSBP; cDC with age and both cSBP and, alternatively, peripheral BP (pBP). Neither pBP nor any of the tested metabolic parameters, including glycated hemoglobin, was associated with PWV and cIMT.

Conclusions: A high proportion of early vascular damage, especially an increased cIMT, is present in children and adolescents with T1D in whom cSBP seems to be a common determinant. In children and adolescents with T1DM, a special focus should be on hemodynamic risk factors beyond metabolic ones.
Safety and Efficacy Using the Second-Generation Cryoballoon in Patients With Atrial Fibrillation and a Common Ostium of Inferior Pulmonary Veins
Authors: Xie Hai-yang , Guo Xiao-gang , Yang Jian-du , Li Jia-hui , Chen Yan-qiao , Cao Zhong-jing , Sun Qi , Li Xiao-yao , Ma Jian
Published: September 2021

Background: Common ostium of inferior pulmonary veins (COIPV) is a kind of pulmonary vein variation. The safety and efficacy of COIPV isolation using the second-generation cryoballoon (CB) ablation remain unknown.

Methods: A total of 10 patients with COIPV from a consecutive series of 1,751 patients with atrial fibrillation (AF) were included. Pulmonary vein isolation (PVI) was performed using the second-generation CB.

Results: The prevalence of a COIPV was 0.57% in this study. PVI was achieved in all pulmonary veins (PVs) without the need for a touch-up. A segmental freeze strategy was applied for each inferior PV, respectively. The mean number of freeze cycles of inferior PVs was 1.4 ± 0.5 for the left inferior pulmonary vein (LIPV), and 2.0 ± 0.9 for the right inferior pulmonary vein (RIPV). Pulmonary vein potential (PVP) of RIPV could not be monitored in real-time in three cases. Eight of 10 patients (80%) were free from atrial arrhythmias without the use of antiarrhythmic drugs during a follow-up period of 23.6 ± 12.9 months. No procedure-related complications occurred in any of the 10 patients.

Conclusions: Common ostium of inferior pulmonary veins is a rare but challenging PV variant. PVI with this unusual anatomic variation using the second-generation 28-mm CB is effective and safe.
Six-Year Follow-Up Outcomes of Catheter Ablation of Para-Hisian Accessory Pathways
Authors: Chen Qingxing , Xu Lili , Zou Tian , Cheng Kuang , Ling Yunlong , Xu Ye , Pang Yang , Liu Guijian , Zhu Wenqing , Ge Junbo
Published: September 2021

Background: Ablation of para-hisian accessory pathways (APs) remains challenging due to anatomic characteristics, and a few studies have focused on the causes for recurrence of radiofrequency ablation of para-hisian APs.

Objective: This retrospective single center study aimed to explore the risk factors for recurrence of para-hisian APs.

Methods: One hundred thirteen patients who had para-hisian AP with an acute success were enrolled in the study. In the 6-year follow-up, 15 cases had a recurrent para-hisian AP. Therefore, 98 patients were classified into the success group, while 15 patients were classified into the recurrence group. Demographic and ablation characteristics were analyzed.

Results: Gender difference was similar in two groups. The median age was 36.2 years old and was younger in the recurrence group. Maximum ablation power was significantly higher in the success group (29 ± 7.5 vs. 22.9 ± 7.8, p < 0.01). Ablation time of final target sites was found to be markedly higher in the success group (123.4 ± 53.1 vs. 86.7 ± 58.3, p < 0.05). Ablation time <60 s was detected in 12 (12.2%) cases in the success group and 7 (46.7%) cases in the recurrence group (p < 0.01). Occurrence of junctional rhythm was significantly higher in the recurrence group (25.5% vs. 53.3%, p < 0.05). No severe conduction block, no pacemaker implantation, and no stroke were reported. Junctional rhythm during ablation (OR = 3.833, 95% CI 1.083–13.572, p = 0.037) and ablation time <60 s (OR = 5.487, 95% CI 1.411–21.340, p = 0.014) were independent risk factors for the recurrence of para-hisian AP.

Conclusions: With careful and accurate mapping, it is relatively safe to ablate para-hisian AP. If possible, proper extension of ablation time could reduce the recurrence rate of para-hisian APs.
Brain-Derived Neurotrophic Factor Mitigates the Association Between Platelet Dysfunction and Cognitive Impairment
Authors: Bélanger Jean-Christophe , Bouchard Véronique , Le Blanc Jessica , Starnino Louisia , Welman Mélanie , Chabot-Blanchet Malorie , Busseuil David , Chertkow Howard , D'Antono Bianca , Lordkipanidzé Marie
Published: September 2021

Background: Platelet hyperactivity is deleterious in coronary artery disease (CAD), requiring lifelong antiplatelet therapy, and is associated with worse cognitive outcomes. Upon activation, platelets release Brain-Derived Neurotrophic Factor (BDNF), a neurotrophin protective against cognitive decline. Given these apparently opposing effects of platelet activation on cognitive health, we investigated whether BDNF levels intercede in the relationship between platelet activation and cognitive function; and whether this relationship is moderated by the presence of CAD.

Methods: In this cross-sectional study, 1,280 participants with (n = 673) and without CAD (n = 607) completed the Montreal Cognitive Assessment (MoCA). Plasma BDNF and soluble P-selectin (a marker of platelet activity) levels were assessed using multiplex flow cytometry.

Results: In a mediation model, platelet activity was correlated with higher plasma BDNF concentrations (b = 0.53, p < 0.0001). The relationship between sP-selectin and BDNF concentrations was stronger for individuals without CAD (b = 0.71, p < 0.0001) than for CAD participants (b = 0.43, p < 0.0001; pinteraction <0.0001). Higher BDNF concentrations were associated with higher MoCA scores (b = 0.26, p = 0.03). The overall effect of platelet activity on cognitive performance was non-significant (total effect: b = −0.12, p = 0.13), and became significant when accounting for BDNF as a mediating factor (direct effect: b = −0.26, p = 0.01). This resulted in a positive indirect effect of platelet activity (via BDNF) on MoCA scores (b = 0.14, CI 95% 0.02–0.30), that was smaller in CAD participants than in non-CAD participants [Δ −0.07 (95% CI −0.14 to −0.01)].

Conclusions: BDNF released from activated platelets could be a mitigating factor in a negative association between platelet activity and cognitive function.
Non-alcoholic Steatohepatitis Pathogenesis, Diagnosis, and Treatment
Authors: Zhu Bo , Chan Siu-Lung , Li Jack , Li Kathryn , Wu Hao , Cui Kui , Chen Hong
Published: September 2021

There has been a rise in the prevalence of non-alcohol fatty liver disease (NAFLD) due to the popularity of western diets and sedentary lifestyles. One quarter of NAFLD patients is diagnosed with non-alcoholic steatohepatitis (NASH), with histological evidence not only of fat accumulation in hepatocytes but also of liver cell injury and death due to long-term inflammation. Severe NASH patients have increased risks of cirrhosis and liver cancer. In this review, we discuss the pathogenesis and current methods of diagnosis for NASH, and current status of drug development for this life-threatening liver disease.