bluuebunny/crossref_metadata_2025 huggingface dataset:
Islamic Critical Thinking: An Analysis of Its Significance Based on The Al-Quran and Scholarly Views
Authors: Junoh Noraini , Mohamad Abdul Manam , Mustafa@Busu Zanirah , Mat Jusoh Nor Asmira
Published: September 2021

Critical thinking is a very important intellectual tool that could help a person form arguments, determine the credibility of sources, analyse presumptions or make decisions in various contexts. Hence, this study intended to examine the Western and Islamic critical thinking concepts as well as its significance according to the al-Quran and the views of scholars. The library research method was used extensively for collecting and analysing data, which was sourced from literature by philosophers, psychologists and Islamic scientists, especially those involved in the cognitive field. The conceptual framework was built using the content analysis method. According on the analysis, the importance of Islamic critical thinking based on the al-Quran and views of scholars in the cognitive field were extensively elaborated to assist in the practice of Islamic critical thinking.  The study found similarities and differences between Islamic and Western critical thinking. The similarities are from the rational utilization aspect and the difference is from the value of truth aspect, whereby Islamic critical thinking accepts divine deliverance (wahyu) as the main source of reference when thinking so that the product of thinking eventually becomes the absolute truth. Hence, the major significance of Islamic critical thinking is to enhance the faith (iman) and piousness (takwa) towards Allah SWT by contemplating and examining nature. At the same time, critical thinking helps a person to face contemporary challenges and solve problems related to every aspect of life. Moreover, critical thinking activities are greatly demanded in Islam so that the mind bestowed by Allah SWT is not neglected and is used properly without transgressing HIS divine deliverance (wahyu).
تطوير الادء الحكومي باستخدام نظم المعلومات الادارية واثرها على الاداء الوظيفي دراسة حالة الاداء الحكومي الفلسطيني
Authors: Alzaanin Mohammed J H , Sulaiman Ibrahim Fahad
Published: September 2021

The transition to using management information systems (MIS) is one of the milestones of modern management transformation. several MIS uses emerged in light of crises, especially during the COVID-19 outbreak. This transition had a great impact on job performance. The current problem statement was the need to clarify the impact of MIS on staff performance and role in enhancing and developing governmental performance in the Palestinian territories. The study aims to show the impact of MIS on the Palestinian government's performance and work development. A descriptive approach was followed to explore published articles relevant to the historical development of governmental performance and the use of MIS. The study showed a significant impact of MIS on performance in general and staff performance in particular. Additionally, the study revealed an early governmental tendency to adopt MIS. Furthermore, the study described the stages of MIS development, which were preliminary and limited followed by a stage of expansion. Also, the study showed a positive MIS impact on job performance, especially during the COVID-19 outbreak. The study recommends continuous work on developing and integrating MIS among various ministries and upgrading databases and applications that enhance performance and facilitate people's lives.
Ketokohan Al-Marbawi: Analisis Perkembangan Pengajian Ilmu Hadis
Authors: Ab Razak Mohd Solleh , Shamsudin Roshimah Shamsudin
Published: September 2021

The recognition as a scholar upon al-Marbawi, whom significantly contributed in the scholarly literatures that which became reference for Muslims within the Malay Archipelagos is undisputed. In spite of the accolades, al-Marbawi was not spared from criticism; in which his background and qualifications in the discipline of hadith were disputed. The arguement stemmed from al-Marbawi's beginnings in the quest for hadith knowledge which was deemed unclear and further aggravated by the void in the details concerning the credence of his teachers. This article therefore aims to study the development of al-Marbawi's pursuit in acquiring his studies from his childhood to adulthood. To achieve these objectives, qualitative research was employed by way of library research in addition to content analysis methods that were fully used in the process of data collection and analysis. The findings show that there are two phases of study al-Marbawi's study of hadith; the basic phase of study being while he was studying in Malaya under the tutelage of Tuan Husin Kedah while the later stage refers to studies in his adulthood which took place in egypt involving formal studies at the al-Azhar University as well as informally through the books of Sahih Muslim and Jami‘ al-Tirmidhi. In summary, the varying periods of study of al-Marbawi proves that he was an authoritative scholar in the discipline of hadith.
Pesta Pongal dan Tahun Baru Cina, Perayaan Adat atau Perayaan Keagamaan? Satu Toleransi Agama di Malaysia
Authors: Mustafar Farrah Wahida , Badhrulhisham Adam
Published: September 2021

The purpose of this study was to examine the celebrations of non-Muslims, namely the Pongal Festival for Hindus and the Chinese New Year for the Chinese community, on whether the Pongal Festival and Chinese New Year are customary or religious festivals and to propose interfaith dialogue as the solution to ensure religious tolerance among the people. This phenomenon highlights the importance of interfaith dialogue to achieve inter-religious tolerance especially for Malaysia consists various races and religions. This literature review study using qualitative method concluded that the Pongal Festival celebrated by Hindus is religious in nature due to the element of worship to the Gods. Meanwhile, Chinese New Year consists of celebrations which can be classified as customary or cultural celebrations. According to the syara’, any act of tasyabbuh in akidah and belief is strictly prohibited. Though the aspect of tasyabbuh needs to be looked further in detail especially in the context of Malaysia as pluralistic-society country. Therefore, inter-religious dialogue, a consensus within the framework of a plural society can be created in a harmonious environment by taking into account the spirit of the Malaysian constitution which celebrates freedom of religion and by considering Islam as the religion of the federation.
Describing a 12-Hour Ambulance Shift during a Second Wave of Covid-19 in London
Authors: Rengers Alexandra , Day Emma , Whitfield Steve
Published: September 2021

The coronavirus disease (COVID-19), caused by the virus SARS-CoV-2, has strained international healthcare systems, including ambulance availability. Ambulance officers and paramedics are at the frontline of this pandemic and are therefore particularly exposed. Under normal operational circumstances, ambulance delivery is challenging; the effects of COVID-19 have exacerbated both the delivery of services and the stress placed on paramedics.

In this case report, we describe a 12-hour emergency ambulance dayshift in central London during the second wave city-wide lockdown. We also discuss the impact COVID-19 has on day-to-day operations and the strategies employed to reduce paramedic infection.
Vuorovaikutus oppimisen kohteena lukiossa – kirja-arvio kolmesta äidinkielen ja kirjallisuuden uudesta oppikirjasarjasta
Authors: Murumäki Suvi-Tuuli
Published: September 2021

Arvioinnin kohteena ovat vuorovaikutusmoduulien materiaalit oppikirjasarjoissa Loisto, Särmä ja Ääni.
Åter till Ålborg
Authors: Parkatti Jarre
Published: September 2021

Flyvbjergs Ålborg-studie har bidragit till förskjutningen från kommunikativ planeringsteori mot poststrukturalism. Den har ändå teoretiska brister som bara delvis utretts. Hans inkoherenta bruk av Foucault och förenklade syn på natur- kontra samhällsvetenskap påverkar alltjämt forskningen. I stället för att söka korrigera defekten avser jag, utan att ogiltigförklara studiens empiriska innehåll, skapa koherens genom att ersätta dess teoretiska grundval med en struktureringsteoretisk, vilket jag även finner teoretiskt fruktbart. I motsats till ett konsekvent foucaultskt perspektiv kan tillgången ta planeringsexpertisen på allvar, liksom Flyvbjerg de facto gör. Hans ambition att lösa tvisten mellan Habermas och Foucault om modernitetens problem måste dock överges.
PENERAPAN METODE KARYA WISATA DALAM PEMBELAJARAN TEMATIK UNTUK MENINGKATKAN PRESTASI BELAJAR IPA SISWA KELAS 1.C SD NEGERI 9 AMPENAN
Authors: Surianah Surianah
Published: September 2021

Penelitian ini dilatar belakangi oleh rendahnya prestasi belajar siswa kelas 1.C SD Negeri 9 Ampenan pada semester I Tahun Pelajaran 2018/2019 yang disebab kan oleh sulitnya siswa memahami materi yang ada pada mata pelajaran IPA. Tujuan penelitian ini adalah untuk meningkatkan  prestasi belajar IPA pada siswa kelas 1.C SD Negeri 9 Ampenan pada semester I Tahun Pelajaran 2018/2019. Instrumen yang digunakan dalam penelitian ini adalah tes prestasi belajar yang dianalisis secara deskriptif.Hasil tes kemampuan awal siswa menunjukkan nilai rata-rata kelas baru mencapai 57,60 dengan presentase ketuntasan belajar sebesar 28%. Hasil tersebut menunjukkan prestasi belajar IPA siswa masih rendah. Setelah diterapkannya metode karya wisata dalam pembelajaran tematik, nilai siswa pada siklus I mencapai 59,20 dengan presentase ketuntasan beajar sebesar 36%. Sedangkan nilai rata-rata di siklus II meningkat menjadi 82,00 dengan presentase ketuntasan belajar mencapai 96%.Hasil yang diperoleh menunjukan adanya peningkatan setelah menggunakan metode karya wisata dalam pembelajaran tematik dan indikator keberhasilan penelitian di capai pada siklus II. Hasil yang telah iperoleh menunjukan bahwa penggunaan metode karya wisata dalam pembelajaran tematik terbukti dapat meningkat kanprestasi belajar siswa pada mata pelajaran IPA. Untuk itu disarankan metode karya wisata dalam pembelajaran temetik dapat dipertimbangkan digunakan dalam pembelajaran dikelas.
PENGGUNAAN METODE SAS DENGAN MEDIA KARTU HURUF UNTUK MENINGKATKAN KETERAMPILAN MEMBACA LANCAR PADA SISWA KELAS 1.C SD NEGERI 9 AMPENAN
Authors: Surianah Surianah
Published: September 2021

Tujuan dari penelitian ini adalah upaya untuk meningkatkan kemampuan membaca siswa kelas 1.C SD Negeri 9 Ampenan, Membaca adalah hal yang di dahulukan karena, dengan membaca anak mulai belajar secara mandiri dengan lebih dini. Tanpa memiliki kemampuan membaca dan menulis yang memadai sejak dini, anak akan mengalami kesulitan belajar di kemudian hari. Dengan membaca kita bisa melihat dunia, dimana kita ketahui kata Belajar merupakan akibat adanya intraksi antara stimulus dan respon. Untuk itu tujuan penelitian ini untuk meningkatkan keterampilan membaca pada siswa kelas satu dengan menggunakan metode sas dengan media kartu huruf.  Sehingga dapat meningkatkan prestas dalam membaca lancar, siswa kelas satu 1.C SD Negeri 9 Ampenan Tahun Pelajaran 2019/2020. Penelitiaan ini menggunakan tahapan-tahapan yang dilakukan Perencanaan, Pembahasan, Observasi dan Refleksi, penelitian ini dilaksanakan dalam dua siklus yaitu siklu I dan siklus II.   Deskripsi hasil dari penlitian ini dapat kita lihat dari masing-masing siklus pada silus I nilai 76,296 (56%) sebyak 14 siswa dari jumlah siswa kelas 1.C sebanya 25 siswa. pada siklus II jumlah nilai 89,636 (92%) sebanyak 23 siswa dari jumlah 25 siswa, hanya 2 orang yang tidak tuntas dalam penelitian ini.  Dapat disimpulkan bahwa dengan metode SAS menggunakan kartu huruf dapat meningkatkan keterampilan membaca lancar pada kelas 1.C SD Negeri 9 Ampenan Tahun Pelajaran 2019/2020. Dapat juga metode SAS ini digunakan dalam pembelajaran selain Bahasa Indonseia.
Mejora de la compraventa de artículos de segundo mano utilizando un entorno de e-commerce
Authors: Köck Elisabeth , Villarreal Vladimir , González Shandy , Vega David , Muñoz Lilia
Published: September 2021

Este artículo tiene como objetivo analizar la comercialización y venta de productos de segunda mano utilizando un entorno de e-commerce, en donde se facilite le econ omía circular en Panamá. Se analizaron algunos trabajos relacionados y la importancia de la economía circular con los Objetivos de Desarrollo Sostenible en el cuidado del medio ambiente. Una vez se analizaron las tecnologías existentes, para el proceso de desarrollo de software se seleccionó la metodología para desarrollo ágil llamada Programación Extrema (Extreme Programming) basándonos en las etapas de planificación, diseño, codificación y pruebas, para crear un prototipo funcional que cumpla con los requerimientos establecidos. Finalmente, se utiliza el método de evaluación heurística para evaluar la usabilidad del prototipo e identificar las mejoras del sistema en trabajos futuros. Este producto nos permitió ofrecer una herramienta tecnológica, que no solo se considera una forma de generación de una idea de negocio, sino que también permite crear conciencia entre los usuarios en aspectos de reutilización y disminución de productos contaminantes.
Sistema de irrigación automático asistido por robot
Authors: Ríos Ana , Hall Andrew , Contreras Kenji , Von Chong Alejandro , Cáceres Danilo
Published: September 2021

Las plantas juegan un rol importante en nuestras vidas, trayéndonos bienestar, mejorando la estética del hogar y brindando beneficios como la purificación del aire, por lo que se desea brindarles el cuidado apropiado, especialmente en el riego continuo y adecuado; tarea que se dificulta de acuerdo con la  cantidad de plantas que se poseen. Con el objetivo de facilitar esta tarea, se propone la creación de un sistema de irrigación automático, que tome mediciones de humedad en la tierra de las plantas de un jardín o huerto, establezca la necesidad de riego y realice esta tarea. El desarrollo del prototipo se divide en los sistemas que lo incorporan, como el sistema de medición, el sistema de riego y sistema de detección de plantas. El resultado es un sistema asistido por un robot que se traslada a lo largo de un jardín tomando mediciones en cada planta y tomando la decisión de regarla o no, activando remotamente un sistema de riego que irriga a cada planta según su necesidad, basado en las lecturas tomadas por el robot. El sistema desarrollado brinda una solución autónoma a un problema presente en la vida de muchas personas, y una herramienta útil en los cultivos para la venta, además de que promueve la sostenibilidad ya que permite hacer uso eficiente del agua para suplir a las plantas la cantidad necesaria para mantener su salud y realizar sus funciones.
Diseño y desarrollo de simulador de un sistema de almacenamiento de energía mediante sensores piezoeléctricos
Authors: Calderón Angélica , Ortega Samantha , Moreno Iveth
Published: September 2021

En este trabajo, se diseñó y desarrolló un simulador que permite realizar estudios mucho más profundos en los generadores eléctricos por vibraciones piezoeléctricas; para ello se partió del comportamiento mecánico de un cristal piezoeléctrico sencillo. Se modeló matemáticamente su funcionamiento, obteniendo un circuito eléctrico equivalente al comportamiento mecánico de estos cristales, posteriormente haciendo uso de NI Multisim 14.0, se simuló un sistema cosechador de energía básico. Para obtener datos certeros y observar la eficiencia de la simulación es necesario hacer uso de un cosechador de energía por medio de vibraciones de forma física, por lo que se construyó un dispositivo de almacenamiento de energía mediante piezoeléctricos desarrollado en investigaciones anteriores, a fin de garantizar que sea un buen instrumento de medición para la captura de las variables necesarias. Finalmente se determinó la ecuación que relaciona la fuerza aplicada a los cristales, con la tensión a la salida del cosechador, para así poder aplicar estos datos a las simulaciones desarrolladas, y calcular el porcentaje de error que posee el simulador.
Impacts of deep-water spills on mesopelagic communities and implications for the wider pelagic food web
Authors: Morzaria-Luna HN , Ainsworth CH , Scott RL
Published: September 2021

Mesopelagic fishes link lower trophic levels and higher predators, as well as production at the surface to the deep sea. Mesopelagic fish may be vulnerable to deep entrained oil plumes of the type seen in the 2010 Deepwater Horizon spill; even at low concentrations, exposure to polycyclic aromatic hydrocarbons (PAHs) may cause lethal and sublethal effects, such as endocrine disruption, growth inhibition, and genetic damage. A reduction in the abundance of mesopelagic fish could potentially shift predation pressure by large pelagics to epipelagic forage or other species, with potential fisheries consequences. We explored this hypothesis on the West Florida Shelf using an Atlantis model for the Gulf of Mexico. Atlantis is a 3-dimensional, spatially explicit marine and coastal modeling framework that incorporates multiple submodels integrating biophysical, chemical, ecological, and fisheries dynamics. We found that biomass, trophic niche width, and predation mortality exerted by mesopelagic predators showed small but varied responses across different contributions of mesopelagics to predator fish diet under oil impacts. We observed shifts in the diet of pelagic predators with increasing availability of mesopelagic fish prey, suggesting that pelagic fish predator populations are more vulnerable to oil exposure if they are tightly coupled to the mesopelagic food web. These results suggest that when measured at the population level, oil-spill impacts may be harder to detect due to the response of individual fish species.
Multimicronutrient supplements in nutrition of pregnant women: critical analysis of research results
Authors: Kodentsova V. M. , Risnik D. V.
Published: September 2021

The purpose of the review is to analyze the results of the use of vitamin-mineral supplements (MMS) during pregnancy using the databases of the RSCI, CyberLeninka, pubMed. The detection of micronutrient deficiency in a significant part of pregnant women requires its unconditional correction by taking vitamin-mineral supplements. In recent years, the emphasis has shifted to studying the effect of MMS intake on the course and outcomes of pregnancy. The effects described in the literature should be treated critically. Most of the studies are based only on a retrospective survey of pregnant women (according to the ‘yes' or ‘no' principle), their supply of micronutrients is not monitored; no causal relationship is established. There is no objective monitoring of the MMS intake. Uncertainties include the composition and doses of micronutrients in the MMS used, the lack of data on drug intake, the assumption that all MMS are equivalent in composition and micronutrient content, and the grouping of women taking MMS with different composition into one group. In addition, the use of incorrect indicators in assessing the physical growth of children occurs. The positive effect of additional intake of MMS is manifested only if initially there was a deficiency of micronutrients.

Conclusions. The intake of MMS during pregnancy improves the supply of vitamins for those women in whose diet there is a lack of them. This prophylaxis reduces the risk of adverse pregnancy outcomes due to vitamin deficiencies.
DUYGUSAL ZEKÂNIN PSİKOLOJİK SAĞLAMLIK ÜZERİNE ETKİSİ: ACİL SAĞLIK HİZMETLERİ PERSONELİ ÜZERİNE BİR ARAŞTIRMA
Authors: TÜRKMEN İbrahim , DOĞAN Hüsamettin Yüce
Published: September 2021

Bu araştırma, acil sağlık hizmetlerinde çalışan personelin duygusal zekâ düzeylerinin psikolojik sağlamlık üzerine etkisini belirlemek amacıyla yapılmıştır. Nicel araştırma olarak tasarlanmış olan araştırmanın evrenini, Uşak ili acil sağlık hizmetleri istasyonunda görev yapan 169 sağlık personeli oluşturmaktadır. Veri toplama süreci 2019 yılı 21 Temmuz-16 Ağustos tarihleri arasında bir ay sürmüş ve 143 sağlık personeli araştırmaya katılmıştır. Verilerin toplanmasında tanıtıcı form, Duygusal Zekâ Ölçeği ve Kısa Psikolojik Sağlamlık Ölçeği kullanılmıştır. Verilerinin analizinde; frekans analizi, t-testi, Anova testi, korelasyon analizi ve regresyon analizi yapılmıştır. Araştırmada katılımcıların duygusal zekâ ölçeği puan ortalamalarının “yüksek”, psikolojik sağlamlık ölçeği puan ortalamalarının ise “orta” düzeyde olduğu bulunmuştur. Erkek katılımcıların psikolojik sağlamlık ölçeği puan ortalamalarının kadın katılımcılara göre daha yüksek olduğu saptanmıştır. Araştırmada, duygusal zekânın psikolojik sağlamlığı istatistiksel olarak anlamlı ve pozitif yönde etkilediği tespit edilmiştir. Duygusal zekânın alt boyutlarından ruh halinin düzenlenmesi (iyimserlik), duyguların değerlendirilmesi ve duyguların kullanımının psikolojik sağlamlığı istatistiksel olarak anlamlı ve pozitif yönde etkilediği görülmüştür. Psikolojik sağlamlık üzerinde en yüksek etkisi bulunan alt boyutun duyguların değerlendirilmesi olduğu tespit edilmiştir. Araştırma sonuçlarına göre, acil sağlık hizmetleri personelinin duygusal zekâsının geliştirilmesinin psikolojik sağlamlıklarını güçlendireceği beklenmektedir.
Unification of Powers: When Effective Lawmakers Sponsor Presidential Proposals in Congress
Authors: Volden Craig , Kernell Samuel , Larocca Roger , Wiseman Alan
Published: September 2021

While scholars have long noted presidential powers over congressional lawmaking arising through persuasion, veto bargaining, and public appeals, we argue that an important tool is missing from this list. Specifically, presidents who are strategic in their choices of early coalition partners in Congress – such as effective sponsors of administration bills – significantly enhance their chance of legislative success. We identify more than 1,400 executive branch proposals appearing as bills in Congress between 1989 and 2006. We examine which members of Congress sponsor these bills, finding strong evidence of disproportionate sponsorship by effective champions, such as majority-party members, committee and subcommittee chairs, lawmakers with proven effectiveness in the previous Congress, party leaders, and senior lawmakers, all else equal. Analyzing the fate of these proposals, we find that much of the success of the president’s agenda in Congress depends on these critical and strategic partnerships with effective congressional proponents.
Do American Voters Really Not Punish Overt Undemocratic Behavior at the Polls? Natural Experimental Evidence from the 2021 Insurrection of the U.S. Capitol
Authors: van Noort Sam
Published: September 2021

Existing research suggests that too few American voters hold politicians electorally accountable for overt undemocratic behavior to reasonably deter democratic backsliding. Evidence for this proposition comes primarily from hypothetical survey experiments with relatively modest treatments. I test this hypothesis using a natural experiment with a powerful real-world treatment: Donald Trump's incitement of the insurrection of the U.S. Capitol on January 6, 2021. The insurrection was unexpected to the general public, did not coincide with other events that could plausibly affect public opinion, and occurred while Gallup was conducting a nationally representative survey using random digit dialing. Comparing Republican Party support among respondents that were interviewed just before, and just after, the insurrection occurred suggests that the insurrection caused a 10.8% decline in support for the Republican Party. Voters predominantly moved to the Democratic Party, rather than Independent. Back-of-the-envelope calculations suggests that this electoral penalty is sufficient to decide presidential elections.
Socialbidragstagares flytt mellan storstad och avfolkningsbygd
Authors: Amcoff Jan
Published: September 2021

Åren kring 2020 dryftas bidragsberoendes flyttmönster i såväl dagspressen som i det offentliga Sverige, men utan att de är särskilt väl kända. Utifrån registerdata konstateras här att kontinuerliga (två år i följd) socialbidragstagare fortfarande är mer flyttbenägna än andra, men att skillnaderna minskar; att nettoströmmen snarast går från kommuner med befolkningsminskning till storstadskommuner, i synnerhet bland kontinuerliga socialbidragstagare med utländsk bakgrund; att de kontinuerliga socialbidragstagare som flyttar från storstad till kommuner med befolkningsminskning har en förhöjd benägenhet att flytta vidare; och att betydelsen av kontinuerligt socialbidragstagande för flyttutbytena mellan storstadskommuner och kommuner med minskande befolkning i stort sett kvarstår även när man kontrollerar för andra attribut i en regressionsmodell. Flyttströmmar antyder alltså huvudsakligen en ”social import” till storstadskommuner från kommuner med befolkningsminskning, snarare än en export i motsatt riktning.
A Reference Database of Standardised Continuous Lumbar Intervertebral Motion Analysis for Conducting Patient-Specific Comparisons
Authors: Breen Alexander , De Carvalho Diana , Funabashi Martha , Kawchuk Greg , Pagé Isabelle , Wong Arnold Y. L. , Breen Alan
Published: September 2021

Lumbar instability has long been thought of as the failure of lumbar vertebrae to maintain their normal patterns of displacement. However, it is unknown what these patterns consist of. Research using quantitative fluoroscopy (QF) has shown that continuous lumbar intervertebral patterns of rotational displacement can be reliably measured during standing flexion and return motion using standardised protocols and can be used to assess patients with suspected lumbar spine motion disorders. However, normative values are needed to make individualised comparisons. One hundred and thirty-one healthy asymptomatic participants were recruited and performed guided flexion and return motion by following the rotating arm of an upright motion frame. Fluoroscopic image acquisition at 15fps was performed and individual intervertebral levels from L2-3 to L5-S1 were tracked and analysed during separate outward flexion and return phases. Results were presented as proportional intervertebral motion representing these phases using continuous means and 95%CIs, followed by verification of the differences between levels using Statistical Parametric Mapping (SPM). A secondary analysis of 8 control participants matched to 8 patients with chronic, non-specific low back pain (CNSLBP) was performed for comparison. One hundred and twenty-seven asymptomatic participants’ data were analysed. Their ages ranged from 18 to 70 years (mean 38.6) with mean body mass index 23.8 kg/m2 48.8% were female. Both the flexion and return phases for each level evidenced continuous change in mean proportional motion share, with narrow confidence intervals, highly significant differences and discrete motion paths between levels as confirmed by SPM. Patients in the secondary analysis evidenced significantly less L5-S1 motion than controls (p < 0.05). A reference database of spinal displacement patterns during lumbar (L2-S1) intersegmental flexion and return motion using a standardised motion protocol using fluoroscopy is presented. Spinal displacement patterns in asymptomatic individuals were found to be distinctive and consistent for each intervertebral level, and to continuously change during bending and return. This database may be used to allow continuous intervertebral kinematics to drive dynamic models of joint and muscular forces as well as reference values against which to make patient-specific comparisons in suspected cases of lumbar spine motion disorders.
An Advanced Systems Pharmacology Strategy Reveals AKR1B1, MMP2, PTGER3 as Key Genes in the Competing Endogenous RNA Network of Compound Kushen Injection Treating Gastric Carcinoma by Integrated Bioinformatics and Experimental Verification
Authors: Zhou Wei , Wu Chao , Zhao Chongjun , Huang Zhihong , Lu Shan , Fan Xiaotian , Tan Yingying , Stalin Antony , You Rongli , Liu Xinkui , Zhang Jingyuan , Wu Zhishan , Wu Jiarui
Published: September 2021

Gastric carcinoma (GC) is a severe tumor of the digestive tract with high morbidity and mortality and poor prognosis, for which novel treatment options are urgently needed. Compound Kushen injection (CKI), a classical injection of Chinese medicine, has been widely used to treat various tumors in clinical practice for decades. In recent years, a growing number of studies have confirmed that CKI has a beneficial therapeutic effect on GC, However, there are few reports on the potential molecular mechanism of action. Here, using systems pharmacology combined with proteomics analysis as a core concept, we identified the ceRNA network, key targets and signaling pathways regulated by CKI in the treatment of GC. To further explore the role of these key targets in the development of GC, we performed a meta-analysis to compare the expression differences between GC and normal gastric mucosa tissues. Functional enrichment analysis was further used to understand the biological pathways significantly regulated by the key genes. In addition, we determined the significance of the key genes in the prognosis of GC by survival analysis and immune infiltration analysis. Finally, molecular docking simulation was performed to verify the combination of CKI components and key targets. The anti-gastric cancer effect of CKI and its key targets was verified by in vivo and in vitro experiments. The analysis of ceRNA network of CKI on GC revealed that the potential molecular mechanism of CKI can regulate PI3K/AKT and Toll-like receptor signaling pathways by interfering with hub genes such as AKR1B1, MMP2 and PTGERR3. In conclusion, this study not only partially highlighted the molecular mechanism of CKI in GC therapy but also provided a novel and advanced systems pharmacology strategy to explore the mechanisms of traditional Chinese medicine formulations.
Serum Uric Acid and Kidney Disease Measures Independently Predict Cardiovascular and Total Mortality: The Uric Acid Right for Heart Health (URRAH) Project
Authors: Russo Elisa , Viazzi Francesca , Pontremoli Roberto , Barbagallo Carlo M. , Bombelli Michele , Casiglia Edoardo , Cicero Arrigo F. G. , Cirillo Massimo , Cirillo Pietro , Desideri Giovambattista , D'Elia Lanfranco , Dell'Oro Raffaella , Ferri Claudio , Galletti Ferruccio , Gesualdo Loreto , Giannattasio Cristina , Iaccarino Guido , Leoncini Giovanna , Mallamaci Francesca , Maloberti Alessandro , Masi Stefano , Mengozzi Alessandro , Mazza Alberto , Muiesan Maria L. , Nazzaro Pietro , Palatini Paolo , Parati Gianfranco , Rattazzi Marcello , Rivasi Giulia , Salvetti Massimo , Tikhonoff Valérie , Tocci Giuliano , Quarti Trevano Fosca A. L. , Ungar Andrea , Verdecchia Paolo , Virdis Agostino , Volpe Massimo , Grassi Guido , Borghi Claudio
Published: September 2021

Background: Serum uric acid predicts the onset and progression of kidney disease, and the occurrence of cardiovascular and all-cause mortality. Nevertheless, it is unclear which is the appropriate definition of hyperuricemia in presence of chronic kidney disease (CKD). Our goal was to study the independent impact of uric acid and CKD on mortality.

Methods: We retrospectively investigated 21,963 patients from the URRAH study database. Hyperuricemia was defined on the basis of outcome specific cut-offs separately identified by ROC curves according to eGFR strata. The primary endpoints were cardiovascular and all-cause mortality.

Results: After a mean follow-up of 9.8 year, there were 1,582 (7.20%) cardiovascular events and 3,130 (14.25%) deaths for all causes. The incidence of cardiovascular and all-cause mortality increased in parallel with reduction of eGFR strata and with progressively higher uric acid quartiles. During 215,618 person-years of follow-up, the incidence rate for cardiovascular mortality, stratified based on eGFR (>90, between 60 and 90 and <60 ml/min) was significantly higher in patients with hyperuricemia and albuminuria (3.8, 22.1 and 19.1, respectively) as compared to those with only one risk factor or none (0.4, 2.8 and 3.1, respectively). Serum uric acid and eGFR significantly interact in determining cardiovascular and all-cause mortality. For each SUA increase of 1 mg/dl the risk for mortality increased by 10% even after adjustment for potential confounding factors included eGFR and the presence of albuminuria.

Conclusions: hyperuricemia is a risk factor for cardiovascular and all-cause mortality additively to eGFR strata and albuminuria, in patients at cardiovascular risk.
A Comparison Between Two Definitions of Contrast-Associated Acute Kidney Injury for Long-Term Mortality in Elderly and Non-elderly Patients After Elective Percutaneous Coronary Intervention
Authors: He Haoming , You Zhebin , Lin Xueqin , He Chen , Zhang Sicheng , Luo Manqing , Lin Maoqing , Zhang Liwei , Lin Kaiyang , Guo Yansong
Published: September 2021

Background: Contrast-associated acute kidney injury (CA-AKI) is responsible for a substantial proportion of the observed mortality that occurs after percutaneous coronary intervention (PCI), particularly in elderly patients. However, there has been significant and debate over whether the optimal definition of CA-AKI persists over prolonged periods due to variations in the prevalence and effects on prognosis. In this study, we aimed to identify whether different definitions of CA-AKI exert differential impacts on long-term mortality when compared between elderly and non-elderly patients receiving elective PCI.

Methods: We prospectively investigated 5,587 consenting patients undergoing elective PCI between January 2012 and December 2018. We considered two classical definitions of CA-AKI from the European Society of Urogenital Radiology (ESUR) and the Acute Kidney Injury Network (AKIN). Multivariable Cox regression analysis was used to investigate the association between CA-AKI and long-term mortality. We also performed interaction and stratified analyses according to age (≤75 or >75 years).

Results: The incidence of CA-AKI according to the ESUR and AKIN definitions was 18.7 and 6.1%, respectively. After a median follow-up of 2.1 years, multivariable Cox regression analysis indicated that CA-AKI according to the AKIN definition was a risk factor for long-term mortality in the overall population [hazard ratio (HR) = 2.20; 95% confidential interval (CI): 1.51–3.22; p < 0.001]; however, this was not the case for the ESUR definition (HR = 1.27; 95% CI: 0.92–1.76; p = 0.153). Further interaction analysis identified a significant interaction between age and the ESUR definition (p = 0.040). Stratified analyses also found an association between the ESUR definition and long-term mortality in patients >75 years of age (p = 0.011), but not in patients ≤75 years of age (p = 0.657).

Conclusion: As a stringent definition of CA-AKI, the AKIN definition was significantly associated with long-term mortality in both non-elderly and elderly patients. However, in elderly patients, the more lenient definition provided by the ESUR was also significantly correlated with long-term mortality, which could sensitively identify high-risk elderly patients and may provide a better alternative.
Diagnosis of Cardiac Involvement in Amyloid A Amyloidosis by Cardiovascular Magnetic Resonance Imaging
Authors: Chamling Bishwas , Drakos Stefanos , Bietenbeck Michael , Klingel Karin , Meier Claudia , Yilmaz Ali
Published: September 2021

Background: Diagnosis of cardiac involvement in amyloid A (AA) amyloidosis is challenging since AA amyloidosis is a rare disease and cardiac involvement even less frequent. The diagnostic yield of currently available non-invasive imaging methods is not well-studied and rather limited, and invasive endomyocardial biopsy (EMB) is rarely performed due to the potential risk of this procedure. Cardiovascular magnetic resonance (CMR)-based myocardial tissue characterization by late-gadolinium-enhancement (LGE) imaging and novel-mapping approaches may increase the diagnostic yield in AA amyloidosis.

Methods: Two patients with AA amyloidosis in whom cardiac involvement was suspected based on CMR findings and subsequently proven by biopsy work-up are presented. CMR studies were performed on a 1.5-T system and comprised a cine steady-state free precession pulse sequence for ventricular function and a late-gadolinium-enhancement (LGE) sequence for detection of myocardial pathology. Moreover, a modified Look-Locker inversion recovery (MOLLI) T1-mapping sequence was applied in basal, mid and apical short-axes prior to contrast agent administration and ~20 min thereafter to determine native T1 and ECV values.

Results: Both patients showed slightly dilated left ventricles (LV) with mild to moderate LV hypertrophy and preserved systolic function. Only a very subtle pattern of LGE was observed in both patients with AA amyloidosis. However, markedly elevated native T1 (max. 1,108 and 1,112 ms, respectively) and extracellular volume fraction (ECV) values (max. 39 and 48%, respectively) were measured in the myocardium suggesting the presence of cardiac involvement - with subsequent EMB-based proof of AA amyloidosis.

Conclusion: We recommend a multi-parametric CMR approach in patients with AA amyloidosis comprising both LGE-based contrast-imaging and T1-mapping-based ECV measurement of the myocardium for non-invasive work-up of suspected cardiac involvement. The respective CMR findings may be used as gatekeeper for additional invasive procedures (such as EMB) and as a non-invasive monitoring tool regarding assessment and modification of ongoing treatments.
Experimental and Numerical Investigation of Characteristics of Highly Heterogeneous Rock Mechanical Responses in Tight Sandy Conglomerate Reservoir Rock Under Tri-axial Compression
Authors: Chen Bin , Ji Jiaqi , Lin Jingqi , Chen Huayong , Wang Xueliang , Guo Xuyang , Yang Wentao , Lin Jiaying
Published: September 2021

Due to the use of horizontal wells and hydraulic fracturing, commercial tight oil production from some tight sandy conglomerate reservoirs has been achieved. Since the widely distributed gravels in the sandy matrix in conglomerate reservoir rocks are harder than the matrix, the rock mechanical response in conglomerates under compression is highly heterogeneous. This increases the complexity of understanding the hydraulic fracturing behaviors in conglomerate reservoirs. Previous tri-axial compression tests provided the stress-strain relationships of conglomerate samples as a whole, and the stress and strain in the gravels and in the sandy matrix were not investigated due to the limitation of the compression test lab. This study presents tri-axial test results for a conglomerate sample cored from a reservoir that has been economically developed. Lab results are then used to calibrate the numerical model for the simulation of the tri-axial compression process. Numerical results indicate that the elastic modulus and size of gravels have significant impacts on the axial stresses and axial strains in the conglomerate. Stress concentrations are observed in gravels due to the heterogeneous mechanical properties in the conglomerate. The reorientation of the maximum horizontal principal stress is quantified to study the mechanisms of the interaction types between hydraulic fractures and gravels embedded in the tight sandy matrix.
The Association Between Genetically Predicted Systemic Inflammatory Regulators and Polycystic Ovary Syndrome: A Mendelian Randomization Study
Authors: Chen Hanxiao , Zhang Yaoyao , Li Shangwei , Tao Yuanzhi , Gao Rui , Xu Wenming , Yang Yihong , Cheng Kemin , Wang Yan , Qin Lang
Published: September 2021

Polycystic ovary syndrome (PCOS) is one of the most common endocrine and metabolic diseases among women of reproductive age. Inflammation may be involved in the pathogenesis of PCOS, but its exact relationship with PCOS remains unclear. Herein, we investigate the causal association between systemic inflammatory regulators and PCOS risk through a two-sample Mendelian randomization (MR) approach based on the latest and largest genome-wide association study (GWAS) of 41 systemic inflammatory regulators in 8293 Finnish participants and a GWAS meta-analysis consisting of 10,074 PCOS cases and 103,164 controls of European ancestry. Our results suggest that higher levels of IL-17 and SDF1a, as well as lower levels of SCGFb and IL-4, are associated with an increased risk of PCOS (OR = 1.794, 95% CI = 1.150 – 2.801, P = 0.010; OR = 1.563, 95% CI = 1.055 – 2.315, P = 0.026; OR = 0.838, 95% CI = 0.712 – 0.986, P = 0.034; and OR = 0.637, 95% CI = 0.413 – 0.983, P = 0.042, respectively). In addition, genetically predicted PCOS is related to increased levels of IL-2 and VEGF (OR = 1.257, 95% CI = 1.022 – 1.546, P = 0.030 and OR = 1.112, 95% CI = 1.006 – 1.229, P = 0.038, respectively). Our results indicate the essential role of cytokines in the pathogenesis of PCOS. Further studies are warranted to assess the possibility of these biomarkers as targets for PCOS prevention and treatment.
Forest Health in Italy: Learning From the Xylella Incursion
Authors: Vettraino Anna Maria , Santini Alberto
Published: September 2021

Italy has an increasing part of its territory covered by forest, particularly prone to invasion by invasive forest pathogens (IFPs) owing to the presence of many different habitats and climates. To be effective, any preventive or management tools to prevent the arrival and establishment of IFPs must be included in the framework of phytosanitary legislation. The European Union has an open-door phytosanitary system meaning that any consignment that is not specifically regulated can enter. Increasing evidence of the limitations and subsequent gaps in biosecurity with the current system. Learning from the recent outbreak of Xylella fastidiosa, we provide comments and suggestions to fill the gaps and improve the phytosanitary system in Italy.
Emerging Advances in Combinatorial Treatments of Epigenetically Altered Pediatric High-Grade H3K27M Gliomas
Authors: Leszczynska Katarzyna B. , Jayaprakash Chinchu , Kaminska Bozena , Mieczkowski Jakub
Published: September 2021

Somatic mutations in histone encoding genes result in gross alterations in the epigenetic landscape. Diffuse intrinsic pontine glioma (DIPG) is a pediatric high-grade glioma (pHGG) and one of the most challenging cancers to treat, with only 1% surviving for 5 years. Due to the location in the brainstem, DIPGs are difficult to resect and rapidly turn into a fatal disease. Over 80% of DIPGs confer mutations in genes coding for histone 3 variants (H3.3 or H3.1/H3.2), with lysine to methionine substitution at position 27 (H3K27M). This results in a global decrease in H3K27 trimethylation, increased H3K27 acetylation, and widespread oncogenic changes in gene expression. Epigenetic modifying drugs emerge as promising candidates to treat DIPG, with histone deacetylase (HDAC) inhibitors taking the lead in preclinical and clinical studies. However, some data show the evolving resistance of DIPGs to the most studied HDAC inhibitor panobinostat and highlight the need to further investigate its mechanism of action. A new forceful line of research explores the simultaneous use of multiple inhibitors that could target epigenetically induced changes in DIPG chromatin and enhance the anticancer response of single agents. In this review, we summarize the therapeutic approaches against H3K27M-expressing pHGGs focused on targeting epigenetic dysregulation and highlight promising combinatorial drug treatments. We assessed the effectiveness of the epigenetic drugs that are already in clinical trials in pHGGs. The constantly expanding understanding of the epigenetic vulnerabilities of H3K27M-expressing pHGGs provides new tumor-specific targets, opens new possibilities of therapy, and gives hope to find a cure for this deadly disease.
Characterization of FMR1 Repeat Expansion and Intragenic Variants by Indirect Sequence Capture
Authors: Grosso Valentina , Marcolungo Luca , Maestri Simone , Alfano Massimiliano , Lavezzari Denise , Iadarola Barbara , Salviati Alessandro , Mariotti Barbara , Botta Annalisa , D’Apice Maria Rosaria , Novelli Giuseppe , Delledonne Massimo , Rossato Marzia
Published: September 2021

Traditional methods for the analysis of repeat expansions, which underlie genetic disorders, such as fragile X syndrome (FXS), lack single-nucleotide resolution in repeat analysis and the ability to characterize causative variants outside the repeat array. These drawbacks can be overcome by long-read and short-read sequencing, respectively. However, the routine application of next-generation sequencing in the clinic requires target enrichment, and none of the available methods allows parallel analysis of long-DNA fragments using both sequencing technologies. In this study, we investigated the use of indirect sequence capture (Xdrop technology) coupled to Nanopore and Illumina sequencing to characterize FMR1, the gene responsible of FXS. We achieved the efficient enrichment (> 200×) of large target DNA fragments (~60–80 kbp) encompassing the entire FMR1 gene. The analysis of Xdrop-enriched samples by Nanopore long-read sequencing allowed the complete characterization of repeat lengths in samples with normal, pre-mutation, and full mutation status (> 1 kbp), and correctly identified repeat interruptions relevant for disease prognosis and transmission. Single-nucleotide variants (SNVs) and small insertions/deletions (indels) could be detected in the same samples by Illumina short-read sequencing, completing the mutational testing through the identification of pathogenic variants within the FMR1 gene, when no typical CGG repeat expansion is detected. The study successfully demonstrated the parallel analysis of repeat expansions and SNVs/indels in the FMR1 gene at single-nucleotide resolution by combining Xdrop enrichment with two next-generation sequencing approaches. With the appropriate optimization necessary for the clinical settings, the system could facilitate both the study of genotype–phenotype correlation in FXS and enable a more efficient diagnosis and genetic counseling for patients and their relatives.
Regulatory Approved Monoclonal Antibodies Contain Framework Mutations Predicted From Human Antibody Repertoires
Authors: Petersen Brian M. , Ulmer Sophia A. , Rhodes Emily R. , Gutierrez-Gonzalez Matias F. , Dekosky Brandon J. , Sprenger Kayla G. , Whitehead Timothy A.
Published: September 2021

Monoclonal antibodies (mAbs) are an important class of therapeutics used to treat cancer, inflammation, and infectious diseases. Identifying highly developable mAb sequences in silico could greatly reduce the time and cost required for therapeutic mAb development. Here, we present position-specific scoring matrices (PSSMs) for antibody framework mutations developed using baseline human antibody repertoire sequences. Our analysis shows that human antibody repertoire-based PSSMs are consistent across individuals and demonstrate high correlations between related germlines. We show that mutations in existing therapeutic antibodies can be accurately predicted solely from baseline human antibody sequence data. We find that mAbs developed using humanized mice had more human-like FR mutations than mAbs originally developed by hybridoma technology. A quantitative assessment of entire framework regions of therapeutic antibodies revealed that there may be potential for improving the properties of existing therapeutic antibodies by incorporating additional mutations of high frequency in baseline human antibody repertoires. In addition, high frequency mutations in baseline human antibody repertoires were predicted in silico to reduce immunogenicity in therapeutic mAbs due to the removal of T cell epitopes. Several therapeutic mAbs were identified to have common, universally high-scoring framework mutations, and molecular dynamics simulations revealed the mechanistic basis for the evolutionary selection of these mutations. Our results suggest that baseline human antibody repertoires may be useful as predictive tools to guide mAb development in the future.