bluuebunny/crossref_metadata_2025 huggingface dataset:
Acoustic and photoacoustic characterization of micron-sized perfluorocarbon emulsions
Authors: M Strohm Eric , Gorelikov Ivan , Matsuura Naomi , Kolios Michael
Published: October 2022

 Perfluorocarbon droplets containing nanoparticles (NPs) have recently been investigated as theranostic and dual-mode contrast agents. These droplets can be vaporized via laser irradiation or used as photoacoustic contrast agents below the vaporization threshold. This study investigates the photoacoustic mechanism of NP-loaded droplets using photoacoustic frequencies between 100 and 1000 MHz, where distinct spectral features are observed that are related to the droplet composition. The measured photoacoustic spectrum from NP-loaded perfluorocarbon droplets was compared to a theoretical model that assumes a homogenous liquid. Good agreement in the location of the spectral features was observed, which suggests the NPs act primarily as optical absorbers to induce thermal expansion of the droplet as a single homogenous object. The NP size and composition do not affect the photoacoustic spectrum; therefore, the photoacoustic signal can be maximized by optimizing the NP optical absorbing properties. To confirm the theoretical parameters in the model, photoacoustic, ultrasonic, and optical methods were used to estimate the droplet diameter. Photoacoustic and ultrasonic methods agreed to within 1.4%, while the optical measurement was 8.5% higher; this difference decreased with increasing droplet size. The small discrepancy may be attributed to the difficulty in observing the small droplets through the partially translucent phantom. 
Perfluorocarbon bubbles as photoacoustic signal amplifiers for cancer theranostics
Authors: Fernandes Donald A. , Kolios Michael
Published: October 2022

Phase change nanoemulsions have been proposed as theranostic agents, using light to induce vaporization into bubbles (also called optical droplet vaporization). The current work uses perfluorohexane nanoemulsions (PFH-NEs) stabilized by a highly biocompatible and optically absorbing fluorosurfactant shell. Once vaporized, the bubbles can be used for contrast enhanced ultrasound (CEUS) imaging but also to enhance photoacoustic (PA) signals due to the presence of bubbles and optical absorbing shell material. The formation and expansion of these gas filled bubbles leads to increasing photoacoustic signals for imaging. Compared to other contrast agents which may not give stable signals due to photo-degradation, these contrast agents are shown to be stable up to 24 hours. The source of PA signal enhancement is through the presence of long lasting perfluorohexane (PFH) bubbles resulting from the optical vaporization. These bubbles generated from the PFH-NEs directly generate photoacoustic signals due to the optical absorption from the fluorosurfactant shell, but also secondary signals from the subsequent scattering of the photoacoustic waves from the PFH bubbles. In addition, the pressures generated from vaporization of NEs and ability to load chemotherapeutic agents enable these nanoparticles to also be used for cancer therapy by contributing to drug delivery and transport. 
Content Analysis of English Activity Books for the First Three Iraqi Primary Stages
Authors: Naser Maysaa Yousif , Hadi Shahla Abdul Kadhim
Published: October 2022

A content analysis of the activity books for the first three Iraqi primary stages has been conducted to determine which thinking skills are addressed in each book and what distributions they follow. A taxonomy of basic thinking skills has been designed to be the tool of analysis. Observation, comprehension, encoding, remembering, and organization are proposed as the lower level skills, while the higher level integrates classification, comparison, application, query, and problem identification. The labels lower and higher imply skills' functionality rather than their inferiority or superiority in comparison to each other. Lower level skills are seen as a base for others, and they involve simpler mental efforts as compared to those in the higher order level. The analysis proves the availability of all the skills in the proposed taxonomy and manifests that their diverse distributions are in harmony with their functional roles as either bases or boosters for other thinking skills.
Mapping Analysis of Development of Digital Book History of Dumai Port Based on Discovery Learning to Increase Historic Awareness of High School Students at Special Purpose State SMA and State SMA 1 Dumai City
Authors: Sarumaha Margaretha Taniria , Sariyatun Sariyatun , Susanto Susanto
Published: October 2022

The purpose of this study is to analyze and map the needs of students and teachers for the development of digital teaching materials, namely the digital book of the history of the port of Dumai City as local history, and see the level of historical awareness of high school students in Dumai City. This research is part of development research (R&D). This type of research is an expo facto research where researchers collect data systematically directly from respondents through data collection instruments. The process of data collection is a critical stage in research. The data that has been collected will be used to test the hypotheses that have been proposed in the study, where the data were obtained through interviews, observations, and questionnaires. The data analysis technique was carried out in a quantitative descriptive manner. The results of the study indicate that (1) there is a positive view of the need for the development of this digital book in the significantly Assisted State Senior High School and Dumai City 1 Public High School; (2) students' learning motivation is still relatively low for history subjects, this is due to the limited use of digital media used in the learning process; (3) history learning media is still very conventional; and (4) students' historical awareness of the existence of local history is still low.
The Late Roman and Early Byzantine Solidi of Scania & the Lund University History Museum
Authors: Fischer Svante
Published: October 2022

This paper is a study of the Late Roman and Early Byzantine solidi from the province of Scania in southern Sweden and the solidi kept in the coin cabinet of the Lund University History Museum. The catalogue lists 34 solidi and classifies the recorded issues according to modern numismatic standards using the current DOC, MIBE and RIC typologies. It is argued that most of the preserved coins from Scania are probably of different types than those originally imported during the solidus influx to Scandinavia. It is more probable than not that the vast majority of solidi imported to Scania in the fifth century came as war booty with returning veterans. As Scania may have had a more hierarchical structure than other parts of Scandinavia, it seems likely that most solidi were recast as ring gold or jewelry in an effort to concentrate wealth and power to inland central places. The few solidi that remain are mainly found along the shorelines of Scania, many of which are looped and have been worn as pendants. As symbolic manifestations of political alliances, these solidi have served a different function than most solidi preserved elsewhere in Scandinavia, notably on neighboring Bornholm, and Öland.
Classification of Coffee Bean Defects Using Gray-Level Co-Occurrence Matrix and K-Nearest Neighbor
Authors: Jumarlis Mila , Mirfan Mirfan , Manga Abdul Rachman
Published: October 2022

Defects in coffee beans can significantly affect the quality of coffee production so that defects in coffee beans can cause a decreasing the level of coffee production. The purpose of this study is to implement the GLCM (gray-level co-occurrence matrix) and the K-NN (k-nearest neighbor) method on a web-based program and provided a website to detect coffee bean defects. This study uses the GLCM algorithm to extract the features of the coffee images and uses the K-NN algorithm to classify the defect level of coffee beans. The system development was built using Unified Modeling Language. The development of this website was utilized the programming structure of PHP, HTML, CSS, Javascript, Mozilla Firefox as a browser for the website and MySql for the database management systems. The results show that the system can provide the output in the form of a classification level of the defect level of the coffee bean images. Then, the accuracy of the coffee bean defect assessment was achieved by 90%. Finally, this study concluded that the proposed system could help the coffee farmers determine the defect level of the coffee beans using images input.
MEMBUAT ALAT CUCI TANGAN OTOMATIS MENGGUNAKAN SENSOR UNTUK PENANGGULANGAN COVID-19 DI RT 01 RW 08 SUKAMAJU BARU TAPOS DEPOK
Authors: Ernawati Siti , Muhammad Agam Satya , Deska Feby Ujianta Hieronimus Emilianus
Published: October 2022

Virus Corona atau sering disebut COVID-19 adalah salah satu Virus yang muncul belakangan ini di Indonesia. Penyebaran virus ini terdeteksi oleh pemerintah pada tanggal 2 maret 2020 yang penyebarannya disebabkan oleh dua orang warga Negara asing asal jepang. Pemerintah lantas membuat pencengahan dengan cara 3M yang artinya Memakai masker, Mencuci tangan, dan Menjaga jarak. Mencuci tangan adalah hal yang paling penting dalam mencegah penyebaran klaster Covid-19 semakin meluas.Akan tetapi pentingnya mencuci tangan disaat pandemi masih belum bisa diterapkan 100% dikarnakan kurangnya fasilitas/tempat cuci tangan yang dapat dijangkau publik secara mudah.Maka dari itu diperlukan alat cuci tangan yang dapat dijangkau secara mudah oleh masyarakat yang dapat mengurangi penyebaran klaster Covid-19 semakin meluas. Sehingga Peneliti menciptakan alat cuci tangan yang menggunakan sensor otomatis yang dapat dipakai masyarakat dalam metode pencegahan penularan Covid-19. Alat cuci tangan ini juga yang akan menarik minat masyarakat untuk tetap menjaga protokol kesehatan dimasa pandemi.
PENGEMBANGAN SISTEM COMPUTER BASED TEST PADA SMK BINTANG HARAPAN CIBARUSAH BEKASI UNTUK PELAKSANAAN UJIAN
Authors: Setiawan Iwan , Suprihatin Heri , Pujiastuti Endang
Published: October 2022

Kondisi pandemi di Indonesia saat ini masih membawa dampak tidak baik untuk semua, termasuk di dalam dunia pendidikan.Saat itu masih melakukan belajar sistem online untuk seluruh siswa. Ujian adalah  salah satu cara yang digunakan sebagai alat untuk mengukur capaian kompetensi siswa secara menyeluruh pada jenjang pendidikan. SMK salah satu lembaga pendidikan, dimana masih menggunakan ujian metode Paper Based Test.  Didalam Pelaksanaan ujian secara Paper Based Test, kertas dapat berpotensi menularkan virus melalui sentuhan tangan, selain itu juga pemborosan, membutuhkan waktu yang lama untuk persiapan soal dan hasil koreksi  untuk mendapatkan nilai lama karena dilakukan secara manual serta berpotensi adanya salah koreksi.  Dengan adanya kondisi tersebut, penulis memberikan solusi tentang sistem ujian menggunakan Computer Based Test. Dengan adanya sistem baru diharapkan dapat meminimalisir wabah covid-19, pembuatan soal ujian lebih cepat, lebih hemat karena tidak pakai kertas, dan siswa memperoleh hasil ujian tidak membutuhkan waktu lama dan tingkat kesalahan koreksi kecil. Bahasa pemrograman yang dipakai dalam aplikasi Computer Based Test adalah bahasa pemrograman JAVA dan database Mysql .Hasil penelitian ini dapat digunakan Guru dan Siswa untuk pelaksanaan ujian secara online di sekolah.
IMPLEMENTASI TES STIFIN DALAM PENENTUAN WALI KELAS UPAYA MENINGKATKAN KOMPETENSI PAEDAGOGIK GURU SD AL WASLIYAH BROMO MEDAN
Authors: Aisyah Siti , Suhendra Suhendra , Ali Yusmar , Wardayani Wardayani
Published: October 2022

Pada masa pandemic Covid 19, Rata- rata siswa diharuskan belajar di rumah hanya dengan online class saja. Berdasarkan hasil observasi ke sekolah SD Al-Wasliyah, Dalam era New Normal saat ini, pihak sekolah telah memperbolehkan siswan bersekolah  dengan cara memberikan jadwal/ gelombang untuk seminggu hanya 3 kali saja. Hal ini yang mengakibatkan Kurangnya pemahaman dan keahlian Wali kelas sebagai ibu di kelas untuk intens dan mengerti kondisi anak. Sehingga SD Al-Wasliyah menerapkan STIFIn tes terhadap semua gurunya, hal ini dikarenakan turunnya kinerja guru, minimnya pendekatan psikologis ke anak. Selama ini Kepala Sekolah hanya mampu menugaskan acak guru-guru yang akan menjadi wali kelas. Sehingga untuk pemetaan Kemampuan kompetensi Paedagogik, Keterampilan, Profesionalitas mereka masih kurang, Karena masih juga ada wali kelas yang belum mampu mengamankan kelas dan melakukan pendekatan ke siswa agar didalam kelas itu minat dan prestasi anak meningkat. Penelitian ini bertujuan untuk mengetahui apa ada hubungan antara STIFIn  dalam meningkatkan Kompetensi Paedagogik dan Profesionalisme guru upaya pemilihan Wali kelas. Dalam Penelitian ini dilaksanakan di SD Al- Wasliyah Bromo Medan, Khususnya untuk guru- guru yang akan diangkat menjadi wali kelas pada tahun ajaran baru mendatang. Sebanyak 14 orang guru, akan di tes dan di uji baik dengan kompetensinya maupun keahliannya dengan STIFIn tes ini.
Northward migration, molting locations, and winter residency of California breeding pigeon guillemots Cepphus columba
Authors: Johns ME , Warzybok P
Published: October 2022

Pigeon guillemots Cepphus columba are ubiquitous along the coasts of the eastern North Pacific, yet little is known about their winter migration patterns, habitat needs, and potential threats faced during the non-breeding period. We used 3 seasons of year-long light level data from tagged individuals to estimate the migration timing and winter residency of pigeon guillemots breeding on Southeast Farallon Island in California (USA). Light level data were combined with a movement model to estimate positions of tagged animals, revealing that individuals from this population undertook a coordinated coastal migration north in the fall, stopping at sites near Haida Gwaii in British Columbia (Canada), presumably during a flightless prebasic molt, before continuing north to stationary overwintering sites in coastal British Columbia and Southeast Alaska. Birds then made an uninterrupted migration south in the spring, returning to waters around Southeast Farallon in late March and early April. Wet/dry data indicated nocturnal resting on land during the breeding season and likely on the water throughout the non-breeding months. This is the first study to confirm the migratory patterns of pigeon guillemots from California, and highlights the importance of the waters of British Columbia and Southeast Alaska for the studied population and possibly other major populations of this species.
Soviet man: the experience of understanding the socio-historical reality
Authors: Toshchenko Zhan T.
Published: October 2022

The article makes an attempt to comprehend appearance of the phenomenon of Soviet man in the historical arena, the specifics of its functioning at various stages of the formation and development of Soviet society. It is shown that the consciousness and activity of the Soviet person developed gradually, within the framework of overcoming objective and subjective contradictory circumstances. Particular attention is paid to the Soviet person as a decisive link in the emergence and existence of a social contract as the basis of Soviet society. A brief critical analysis of anti-Soviet concepts is being implemented. A search is being made for an answer to the question why the phenomenon of the Soviet man continues to live in the minds and hearts of Russians three decades after the collapse of the Soviet Union.
Siyasi İktidarın Sınırlandırılması ve Anayasal Denge Denetimi Düşüncesinin Kökeni
Authors: ARIKAN Cengiz , YARIMBATMAN Güven
Published: October 2022

Sahip olduğu güç kullanma tekeli ile diğer iktidarlardan farklı olan siyasal iktidar, bir yandan toplumun devamını sağlarken, öte yandan bu gücün kötüye kullanımı tehlikesini içinde barındırır. Siyasal iktidarın sahip olduğu gücün kötüye kullanımını ve bunun yıkıcı sonuçlarını engellemenin yolu, ancak bu iktidarın sınırlandırılması, dengelenmesi ve denetlenmesiyle mümkündür. Özgürlüğünün ve güvenliğinin kayıt altına alınmış bir iktidardan geçtiğinin bilincinde olan insanoğlu, siyasi iktidarın ortaya çıkmasından bugüne, bu iktidarı sınırlandırmanın araçlarını ve kurallarını bulmaya çabalamıştır. Antik Yunanla başlayan bu düşünsel çaba, modern devletin ortaya çıkmasıyla başka bir boyut kazanmış, tarihin ilk yazılı anayasası kabul edilen Amerikan Anayasası’nın yapıcıları, yazmış oldukları anayasayla getirdikleri frenler ve dengeler adı verilen bir sistemle, bu düşünsel mirasa önemli katkılar sunmuşlardır. Her bir erkin, bir diğer erk üzerinde bazı etkilere sahip olmasını ifade eden frenler ve dengeler sistemi, Amerika Birleşik Devletleri başkanlık sistemini başarılı kılan en önemli unsurdur. Bu çalışmada, siyasal iktidarın sınırlandırılması ve anayasal denge denetimin yalnızca düşünsel kökenleri incelenmiş, iktidarı sınırlandırmanın, denge ve denetimin araçlarına yer verilmemiştir. Anayasal denge ve denetleme, 2017 anayasa değişikliği ile başka adlarla anılsa da fiilen başkanlık sistemine geçilen Türkiye’nin de güncel meselelerindendir.
Conservative Treatment of Low Back Pain with Incidental Finding of Diffuse Idiopathic Skeletal Hyperostosis: A Case Report
Authors: LaCourt Shawn , Shaw Trevor
Published: October 2022

Low back pain affects 630 million people worldwide and may result in a physical, social, or psychological liability to those people [1]. Patients with lower back pain commonly will have a higher incidence of functional disability, psychosocial issues, and decreased work productivity [1]. The clinician muscle must provide the correct course of treatment for the patient, clinician [2]. Diffuse idiopathic skeletal hyperostosis (DISH) is a noninflammatory condition resulting from a pathologic calcification and ossification of areas of the spine and possibly other joints [3]. Several risk factors in developing DISH are advanced age, hypertension, diabetes, obesity, and genetics [4,5]. Individuals with DISH are typically asymptomatic; however, a study of two hundred individuals diagnosed with DISH demonstrated that 72% were experiencing back pain and 84% reported overall spinal stiffness [3,4]. Diffuse idiopathic skeletal hyperostosis is an incidental finding in imaging in which the pathogenesis is currently not known [3,4]. To diagnose DISH in the spine it is required to observe at least three bony bridges at the anterolateral spine [4]. The bony bridges are viewed as osteophytes on the anterior portion of the spine [3]. DISH in the cervical spine may lead to symptoms such as dysphagia or upper airway obstruction [3]. Additionally, in the spine DISH has been linked to compression of neural structures resulting in myeloradiculopathy [3]. Structurally, this can lead to spinal stenosis, and spinal cord or nerve root compression [3].Currently, there is one published article describing chiropractic treatment of DISH with flexion distraction technique [6]. Al-Herz et al. [7] discussed exercise therapy for patients with DISH. Additionally, Le et al. [3] discussed, briefly, several strategies for the management of DISH. Current literature does not combine instrument-assisted manipulation, soft tissue therapy, and exercise therapy for the management of DISH. Therefore the purpose of this article is to demonstrate the effectiveness of exercise and manual therapy for the treatment of DISH related pain and dysfunction.
Quality Indicators for Chronic Diseases in Primary Care
Authors: Caylan Ayse , Paspal Busra , Dagdeviren Hamdi Nezih
Published: October 2022

Quality indicators is defined as nominal, ordinal or quantitative measures of health care quality in order to provide effective, safe and human-centered health care. They are the most important tools in monitoring quality. Quality indicators are widely used in many countries, including Türkiye, to evaluate and improve the quality of care in the health system.

Quality indicators in primary care in Türkiye started to be implemented in 2017 by the Ministry of Health with the Organization for Economic Cooperation and Development Health Care Quality Indicators Turkey project. According to this project Turkey includes 9 categories. These are Primary Health Care (preventable hospital admissions), Primary Care (prescribing), Acute Care, Mental Health Services, Patient Safety, Patient Experiences, Cancer Care, Infectious Disease Care, Dementia Health Services.

The Category of Primary care has seven quality indicators. Although it was introduced in 2017 it is not widely used in primary care.

Primary care plays an important role in the promotion of health care. Therefore, using quality indicators will be helpful in this process.

Keywords: chronic disease, family physician, quality ındicators, health care
Shifting knowledge practices for sustainable land use: Insights from producers of Aotearoa New Zealand
Authors: Kirk Nicholas , Duncan Ronlyn , Booth Pamela , Robson-Williams Melissa
Published: October 2022

Governments have been introducing regulations alongside sustainability-focused incentives, programs, and policies to help address environmental issues associated with agriculture. In this new ecological and policy context, where the socio-economic consequences of environmental limits are beginning to be experienced, old questions are being asked about how agricultural producers engage with advice and advisors and what factors might facilitate a faster transition to more sustainable land use. This paper presents research from Aotearoa New Zealand where a nationwide survey and focus groups have examined how producers are using advisory services. The research draws on the ‘triggering change’ cycle to explain how imperatives to shift to more sustainable land use are changing the knowledge practices of producers and their relationships with farm advisors. The research highlights the importance of conceiving producers as curators of advice and information rather than mere recipients, which involves doing their own research to identify what role they want an advisor to play. These findings have important implications for the development of future extension programs to help producers adopt, adapt and/or co-design more sustainable land use practices.
Past, present, and future perspectives of biodegradable films for soil: A 30-year systematic review
Authors: Sun Yitao , Yang Wenlong , Shi Hongxia , Tanveer Sikander Khan , Hai Jiangbo
Published: October 2022

Based on the Web of Science Core Collection (WOSCC) database, the academic works published in the past 30 years on biodegradable films for soil were analyzed. In order to ensure the rigor of this experiment, this paper is based on the mathematical double matrix model VOS Viewer software and CiteSpace software. This work shows that publications of biodegradable films for soil are increasing year by year; polymer science is the hottest subject in the field of biodegradable films for soil; China and the United States are the countries with the most significant number of publications in this field, has an important position; Washington State University is the most published institution. This study further identifies and reveals the essential characteristics, research strength, knowledge structure, main research fields, and research hotspots in the late stage of the field of biodegradable films for soil and introduces the Activity Index (AI) and the Attractive Index (AAI), thereby assessing trends and performance in different countries. The paper also further illustrates the importance of biodegradable films by presenting field trials using biodegradable films on different plants. The research in the field of biodegradable films for soil is divided into four categories: “The research field of degradation,” “The effect of biodegradable film on soil,” “Performance and mechanism of the biodegradable film,” and “Effects of biodegradable film on crop growth and development.”. The study can be seen as a microcosm of the development of biodegradable films for soils, which will help researchers quickly identify their general patterns. Readers can better understand the changes and development trends in this field in the past 30 years and provide references for future research.
Therapeutic modulation of gene expression in the disease state: Treatment strategies and approaches for the development of next-generation of the epigenetic drugs
Authors: Rittiner Joseph , Cumaran Mohanapriya , Malhotra Sahil , Kantor Boris
Published: October 2022

Epigenetic dysregulation is an important determinant of many pathological conditions and diseases. Designer molecules that can specifically target endogenous DNA sequences provide a means to therapeutically modulate gene function. The prokaryote-derived CRISPR/Cas editing systems have transformed our ability to manipulate the expression program of genes through specific DNA and RNA targeting in living cells and tissues. The simplicity, utility, and robustness of this technology have revolutionized epigenome editing for research and translational medicine. Initial success has inspired efforts to discover new systems for targeting and manipulating nucleic acids on the epigenetic level. The evolution of nuclease-inactive and RNA-targeting Cas proteins fused to a plethora of effector proteins to regulate gene expression, epigenetic modifications and chromatin interactions opened up an unprecedented level of possibilities for the development of “next-generation” gene therapy therapeutics. The rational design and construction of different types of designer molecules paired with viral-mediated gene-to-cell transfers, specifically using lentiviral vectors (LVs) and adeno-associated vectors (AAVs) are reviewed in this paper. Furthermore, we explore and discuss the potential of these molecules as therapeutic modulators of endogenous gene function, focusing on modulation by stable gene modification and by regulation of gene transcription. Notwithstanding the speedy progress of CRISPR/Cas-based gene therapy products, multiple challenges outlined by undesirable off-target effects, oncogenicity and other virus-induced toxicities could derail the successful translation of these new modalities. Here, we review how CRISPR/Cas—based gene therapy is translated from research-grade technological system to therapeutic modality, paying particular attention to the therapeutic flow from engineering sophisticated genome and epigenome-editing transgenes to delivery vehicles throughout efficient and safe manufacturing and administration of the gene therapy regimens. In addition, the potential solutions to some of the obstacles facing successful CRISPR/Cas utility in the clinical research are discussed in this review. We believe, that circumventing these challenges will be essential for advancing CRISPR/Cas-based tools towards clinical use in gene and cell therapies.
The emerging role of cancer nanotechnology in the panorama of sarcoma
Authors: Mercatali Laura , Vanni Silvia , Miserocchi Giacomo , Liverani Chiara , Spadazzi Chiara , Cocchi Claudia , Calabrese Chiara , Gurrieri Lorena , Fausti Valentina , Riva Nada , Genovese Damiano , Lucarelli Enrico , Focarete Maria Letizia , Ibrahim Toni , Calabrò Luana , De Vita Alessandro
Published: October 2022

In the field of nanomedicine a multitude of nanovectors have been developed for cancer application. In this regard, a less exploited target is represented by connective tissue. Sarcoma lesions encompass a wide range of rare entities of mesenchymal origin affecting connective tissues. The extraordinary diversity and rarity of these mesenchymal tumors is reflected in their classification, grading and management which are still challenging. Although they include more than 70 histologic subtypes, the first line-treatment for advanced and metastatic sarcoma has remained unchanged in the last fifty years, excluding specific histotypes in which targeted therapy has emerged. The role of chemotherapy has not been completely elucidated and the outcomes are still very limited. At the beginning of the century, nano-sized particles clinically approved for other solid lesions were tested in these neoplasms but the results were anecdotal and the clinical benefit was not substantial. Recently, a new nanosystem formulation NBTXR3 for the treatment of sarcoma has landed in a phase 2-3 trial. The preliminary results are encouraging and could open new avenues for research in nanotechnology. This review provides an update on the recent advancements in the field of nanomedicine for sarcoma. In this regard, preclinical evidence especially focusing on the development of smart materials and drug delivery systems will be summarized. Moreover, the sarcoma patient management exploiting nanotechnology products will be summed up. Finally, an overlook on future perspectives will be provided.
The impact of ethnicity and intra-pancreatic fat on the postprandial metabolome response to whey protein in overweight Asian Chinese and European Caucasian women with prediabetes
Authors: Joblin-Mills Aidan , Wu Zhanxuan , Fraser Karl , Jones Beatrix , Yip Wilson , Lim Jia Jiet , Lu Louise , Sequeira Ivana , Poppitt Sally
Published: October 2022

The “Thin on the Outside Fat on the Inside” TOFI_Asia study found Asian Chinese to be more susceptible to Type 2 Diabetes (T2D) compared to European Caucasians matched for gender and body mass index (BMI). This was influenced by degree of visceral adipose deposition and ectopic fat accumulation in key organs, including liver and pancreas, leading to altered fasting plasma glucose, insulin resistance, and differences in plasma lipid and metabolite profiles. It remains unclear how intra-pancreatic fat deposition (IPFD) impacts TOFI phenotype-related T2D risk factors associated with Asian Chinese. Cow’s milk whey protein isolate (WPI) is an insulin secretagogue which can suppress hyperglycemia in prediabetes. In this dietary intervention, we used untargeted metabolomics to characterize the postprandial WPI response in 24 overweight women with prediabetes. Participants were classified by ethnicity (Asian Chinese, n=12; European Caucasian, n=12) and IPFD (low IPFD < 4.66%, n=10; high IPFD ≥ 4.66%, n=10). Using a cross-over design participants were randomized to consume three WPI beverages on separate occasions; 0 g (water control), 12.5 g (low protein, LP) and 50 g (high protein, HP), consumed when fasted. An exclusion pipeline for isolating metabolites with temporal (T0-240mins) WPI responses was implemented, and a support vector machine-recursive feature elimination (SVM-RFE) algorithm was used to model relevant metabolites by ethnicity and IPFD classes. Metabolic network analysis identified glycine as a central hub in both ethnicity and IPFD WPI response networks. A depletion of glycine relative to WPI concentration was detected in Chinese and high IPFD participants independent of BMI. Urea cycle metabolites were highly represented among the ethnicity WPI metabolome model, implicating a dysregulation in ammonia and nitrogen metabolism among Chinese participants. Uric acid and purine synthesis pathways were enriched within the high IPFD cohort’s WPI metabolome response, implicating adipogenesis and insulin resistance pathways. In conclusion, the discrimination of ethnicity from WPI metabolome profiles was a stronger prediction model than IPFD in overweight women with prediabetes. Each models’ discriminatory metabolites enriched different metabolic pathways that help to further characterize prediabetes in Asian Chinese women and women with increased IPFD, independently.
Mechanisms of estrogen deficiency-induced osteoporosis based on transcriptome and DNA methylation
Authors: Xu Ziying , Yu Zihui , Chen Ming , Zhang Mingming , Chen Ruijing , Yu Haikuan , Lin Yuan , Wang Duanyang , Li Shang , Huang Ling , Li Yi , Yuan Jing , Yin Pengbin
Published: October 2022

Osteoporosis is a disease that impacts the elderly. Low estrogen is related to changes in DNA methylation and consequent alterations in gene expression, leading to a new direction in research related to the pathophysiology of osteoporosis. We constructed an Ovariectomized (OVX) mouse model in our study, and the mouse models had osteoporosis based on the phenotype and methylation levels in the mouse’s bone. Furthermore, the methylation level of the OVX mice was significantly changed compared to that of SHAM mice. Therefore, we performed genome-level analysis on the mouse model using transcriptome and Whole Genome Bisulfite Sequencing (WGBS) by combining the data of two omics and discovered that the changes in gene expression level caused by osteoporosis primarily focused on the decrease of bone and muscle development and the activation of the immune system. According to intersection analysis of methylation and transcriptome data, the differentially expressed genes and pathways are consistent with the differentially expressed methylation locations and regions. Further, the differentially expressed methylation sites were mainly concentrated in promoters, exons, and other critical functional regions of essential differentially expressed genes. This is also the primary cause of gene differential expression variations, indicating that estrogen deficiency might regulate gene expression by altering methylation modification, leading to osteoporosis. We demonstrated the clinical value of methylation modification research, and these findings would improve the current understanding of underlying molecular mechanisms of osteoporosis incidence and development and provide new ideas for early detection and treatment of osteoporosis.
Miro1 depletion disrupts spatial distribution of mitochondria and leads to oocyte maturation defects
Authors: Lee In-Won , Adhikari Deepak , Carroll John
Published: October 2022

Mitochondria are dynamic organelles that undergo regulated microtubule- and actin-mediated trafficking to meet local energy and metabolic needs. Mitochondrial trafficking may be particularly critical in large cells such as eggs and early embryos where spindle formation and polar body extrusion occur in specific regions of the cytoplasm. To investigate the role of mitochondrial distribution in oocytes we have targeted the mitochondrial membrane protein, MIRO1, which couples mitochondria to the motor protein-TRAK complex. Oocyte-specific deletion of MIRO1 leads to the formation of large aggregates of mitochondria in perinuclear and cortical compartments. Mitochondria remain capable of long-range trafficking during maturation, indicating redundancy in the mechanisms coupling mitochondria to motor proteins. Polar body extrusion in the absence of MIRO1 was reduced by approximately 20%. In MIRO1-deleted zygotes, mitochondria showed increased accumulation around the pronuclei but this did not affect mitochondrial distribution to daughter blastomeres. In vitro development of parthenogenetic embryos was also reduced, although no differences were found in the fertility of oocyte-specific Miro1 KO mice. These findings demonstrate MIRO1 acts as a mitochondrial adaptor, setting mitochondrial distribution in oocytes and early embryos, and disrupting this process compromises in vitro oocyte maturation and embryo development.
Diagnostic accuracy and limit of detection of ten malaria parasite lactate dehydrogenase-based rapid tests for Plasmodium knowlesi and P. falciparum
Authors: Tan Angelica F. , Sakam Sitti Saimah binti , Rajahram Giri S. , William Timothy , Abd Rachman Isnadi Mohammad Faruq , Daim Sylvia , Barber Bridget E. , Kho Steven , Sutherland Colin J. , Anstey Nicholas M. , Yerlikaya Seda , van Schalkwyk Donelly A. , Grigg Matthew J.
Published: October 2022

Background

Plasmodium knowlesi causes zoonotic malaria across Southeast Asia. First-line diagnostic microscopy cannot reliably differentiate P. knowlesi from other human malaria species. Rapid diagnostic tests (RDTs) designed for P. falciparum and P. vivax are used routinely in P. knowlesi co-endemic areas despite potential cross-reactivity for species-specific antibody targets.

Methods

Ten RDTs were evaluated: nine to detect clinical P. knowlesi infections from Malaysia, and nine assessing limit of detection (LoD) for P. knowlesi (PkA1-H.1) and P. falciparum (Pf3D7) cultures. Targets included Plasmodium-genus parasite lactate dehydrogenase (pan-pLDH) and P. vivax (Pv)-pLDH.

Results

Samples were collected prior to antimalarial treatment from 127 patients with microscopy-positive PCR-confirmed P. knowlesi mono-infections. Median parasitaemia was 788/µL (IQR 247-5,565/µL). Pan-pLDH sensitivities ranged from 50.6% (95% CI 39.6–61.5) (SD BIOLINE) to 87.0% (95% CI 75.1–94.6) (First Response® and CareStart™ PAN) compared to reference PCR. Pv-pLDH RDTs detected P. knowlesi with up to 92.0% (95% CI 84.3-96.7%) sensitivity (Biocredit™). For parasite counts ≥200/µL, pan-pLDH (Standard Q) and Pv-pLDH RDTs exceeded 95% sensitivity. Specificity of RDTs against 26 PCR-confirmed negative controls was 100%. Sensitivity of six highest performing RDTs were not significantly different when comparing samples taken before and after (median 3 hours) antimalarial treatment. Parasite ring stages were present in 30% of pre-treatment samples, with ring stage proportions (mean 1.9%) demonstrating inverse correlation with test positivity of Biocredit™ and two CareStart™ RDTs.

For cultured P. knowlesi, CareStart™ PAN demonstrated the lowest LoD at 25 parasites/µL; LoDs of other pan-pLDH ranged from 98 to >2000 parasites/µL. Pv-pLDH LoD for P. knowlesi was 49 parasites/µL. No false-positive results were observed in either P. falciparum-pLDH or histidine-rich-protein-2 channels.

Conclusion

Selected RDTs demonstrate sufficient performance for detection of major human malaria species including P. knowlesi in co-endemic areas where microscopy is not available, particularly for higher parasite counts, although cannot reliably differentiate among non-falciparum malaria.
Flavobacterium columnare ferric iron uptake systems are required for virulence
Authors: Conrad Rachel A. , Evenhuis Jason P. , Lipscomb Ryan S. , Pérez-Pascual David , Stevick Rebecca J. , Birkett Clayton , Ghigo Jean-Marc , McBride Mark J.
Published: October 2022

Flavobacterium columnare, which causes columnaris disease, is one of the costliest pathogens in the freshwater fish-farming industry. The virulence mechanisms of F. columnare are not well understood and current methods to control columnaris outbreaks are inadequate. Iron is an essential nutrient needed for metabolic processes and is often required for bacterial virulence. F. columnare produces siderophores that bind ferric iron for transport into the cell. The genes needed for siderophore production have been identified, but other components involved in F. columnare iron uptake have not been studied in detail. We identified the genes encoding the predicted secreted heme-binding protein HmuY, the outer membrane iron receptors FhuA, FhuE, and FecA, and components of an ATP binding cassette (ABC) transporter predicted to transport ferric iron across the cytoplasmic membrane. Deletion mutants were constructed and examined for growth defects under iron-limited conditions and for virulence against zebrafish and rainbow trout. Mutants with deletions in genes encoding outer membrane receptors, and ABC transporter components exhibited growth defects under iron-limited conditions. Mutants lacking multiple outer membrane receptors, the ABC transporter, or HmuY retained virulence against zebrafish and rainbow trout mirroring that exhibited by the wild type. Some mutants predicted to be deficient in multiple steps of iron uptake exhibited decreased virulence. Survivors of exposure to such mutants were partially protected against later infection by wild-type F. columnare.
Unconscious load changer: Designing method to subtly influence load perception by simply presenting modified myoelectricity sensor information
Authors: Futami Kyosuke , Seki Tomoya , Murao Kazuya
Published: October 2022

Systems of presenting myoelectricity sensor information allow users to understand the body's load for various purposes, such as medical rehabilitation and sports training. If there is a method to create the psychological phenomenon of unconsciously increasing or decreasing a user's load perception simply by changing how to present the myoelectricity sensor values, it will help design a more effective system. Therefore, we propose a method to manipulate load perception by presenting modified myoelectricity sensor information. The proposed method aims to induce higher or lower load perception by modifying the actual myoelectric value to a higher or lower value. We implemented a prototype system and evaluated our method for the two types of load perception of weight perception and fatigue perception when handling objects. The result showed that most subjects unconsciously increased or decreased their load perception to match the presented myoelectric value, while the minority subjects got the opposite response from the majority subjects. This result indicates the feasibility of user assistance systems that use this phenomenon for a good purpose, such as systems that slightly reduce the load perception during physical activity. On the other hand, this result also indicates the feasibility of systems that use this phenomenon for a bad purpose, such as systems that increase user's fatigue to harm user's activity. This study provides helpful findings for designing and using sensor information presentation systems considering the psychological phenomenon.
Patient experience of post-extraction pain management
Authors: Truitt Anjali R. , Asche Stephen E. , Ziegenfuss Jeanette Y. , Mitchell Shannon G. , Gryczynski Jan , Kane Sheryl M. , Worley Donald C. , Rindal D. Brad
Published: October 2022

Introduction

Few studies have assessed the impact of clinical decision support, with or without patient education, on patient-reported outcomes in dentistry. This cross-sectional survey was conducted to understand patients' experience with shared decision-making and pain management associated with a tooth extraction.

Methods

We administered a phone survey to 981 adult patients within a week of having a tooth extraction. The tooth extraction was performed at a large regional dental practice by a dentist participating in a randomized controlled trial of a clinical decision support system to reduce reliance on opioids for tooth extraction-related pain management. The survey compared respondents' answers by study arm: standard practice (SP) or clinical decision support with (CDS-E) or without patient education (CDS).

Results

Of respondents (n = 492, response rate: 52%), 91% reported that their dental provider talked about what to expect for pain in the days following the extraction, 92% stated that their dental provider talked about how to treat post-extraction pain, and 74% expressed they were confident in their ability to manage post-extraction pain at the end of the extraction visit. We found no statistically significant differences in patient responses across study arms for average pain in the 3 days following the extraction (p = 0.65, CDS vs. SP; p = 0.41, CDS-E vs. SP) or in shared decision-making (p = 0.38, CDS vs. SP; p = 0.70, CDS-E vs. SP).

Conclusion

Most patients reported adequate pain management and shared decision-making about pain management related to their tooth extraction. Further research will assess differences in analgesic recommendations across study arms.
Cultural resources, academic self-concept, and achievement of chemistry students in senior secondary schools of Calabar Municipality, Cross River State, Nigeria
Authors: Nja Cecilia Obi , Ukwetang John Okpa , Orim Richard Ekonesi , Neji Hope Amba , Edu Grace Onya , Ukah Julius Ukah , Olofu Martin Afen
Published: October 2022

This paper investigated cultural resources, academic self-concept, and achievement of chemistry students in a senior secondary school in Nigeria. Research questions and hypotheses were formulated to direct the study. A quasi-experimental factorial design was used in this study, which had a sample size of 90 senior secondary chemistry students. The Academic Self-concept Questionnaire (ASCQ) and Chemistry Achievement Test (CAT) were used in this study. The reliability of ASCQ was done using Cronbach Alpha and it was 0.80 while the reliability of CAT was done using Kuder Richardson formula 20 and had a coefficient of 0.79. The results obtained were analyzed using a dependent t-test and analysis of variance (ANCOVA). Analysis of data showed that the academic self-concept of the students increased after using cultural resources and the experimental group gained more than the control. This study found that cultural resources made the learning of chemical concepts easy to comprehend as the materials were things that the learners were familiar with. This study recommends, among others, that teachers use cultural resources in teaching chemistry.
The effect of COVID-19 on the presentation of thyroid disease in children
Authors: McCowan Rebecca , Wild Edith , Lucas-Herald Angela K. , McNeilly Jane , Mason Avril , Wong Sze Choong , Ahmed S. Faisal , Shaikh M. Guftar
Published: October 2022

Introduction

Although studies suggest a potential link between COVID-19 and thyroid dysfunction in adults, there are insufficient data to confirm that association in children, and whether there is any effect on presentation to healthcare services.

Aims

To identify whether presentations of thyroid dysfunction in children to a tertiary paediatric hospital changed as a result of the COVID-19 pandemic.

Methods

A retrospective case note review was conducted of all children with abnormal thyroid function tests between 1st January 2016 and 31st December 2021 at a tertiary paediatric endocrine centre in the United Kingdom.

Results

Overall, 244 children whose first presentation was within the timeframe of interest were included in this study, with a median age (range) of 11.5 (6.1, 16.8) years. Of these, 43 (18%) were hyperthyroid and 201 (82%) were hypothyroid. The greatest number of thyroid presentations occurred in 2021 (n=60, 25% of total over time period) and the fewest in 2020 (n=10, 4% of total over time period). Prior to this, the median (range) number of presentations per year was 34 (28, 39). There were no statistically significant differences in biochemistry, antibody status or other clinical characteristics between those who presented with hyperthyroidism prior to the pandemic or after. In those with hypothyroidism, baseline biochemistry was similar between the 2 groups, but the presence of other autoimmune conditions was greater pre-pandemic (17.2% vs 15.0%, p=0.03). In addition, patients were more likely to have transient thyroid dysfunction, which did not require treatment post-pandemic (70.0% vs 49.6%, p=0.0086).

Conclusions

Although overall rates of presentation with thyroid dysfunction have not altered since the first wave of the COVID-19 pandemic, presentations with transient thyroid dysfunction, not requiring ongoing treatment have increased. Further research regarding the relationship between COVID-19 and thyroid function in children and young people, is needed.